Macrocyclic bifunctional chelants, complexes thereof and their antibody conjugates

Abstract: A group of functionalized polyaminocarboxylate chelants that form complexes with rare earth-type metal ions are disclosed. The complexes can be covalently attached to an antibody or antibody fragment and used for therapeutic and/or diagnostic purposes.

Description: Functionalized chelants, or bifunctional coordinators, are known to be capable of being covalently attached to an antibody having specificity for cancer or tumor cell epitopes or antigens. Radionuclide complexes of such antibody/chelant conjugates are useful in diagnostic and/or therapeutic applications as a means of conveying the radionuclide to a cancer or tumor cell. See, for example, Meares et al., Anal. Biochem. 142 , 68-78, (1984); and Krejcarek et al., Biochem. and Biophys. Res. Comm. 77 , 581-585 (1977). Aminocarboxylic acid chelating agents have been known and studied for many years. Typical of the aminocarboxylic acids are nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), hydroxyethylethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexanetetraacetic acid (CDTA) and 1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA). Numerous bifunctional chelating agents based on aminocarboxylic acids have been proposed and prepared. For example the cyclic dianhydride of DTPA [Hnatowich et al. Science 220 , 613-615, (1983); U.S. Patent 4,479,930] and mixed carboxycarbonic anhydrides of DTPA [Gansow, U.S. Patents 4,454,106 and 4,472,509; Krejcarek et al., Biochem. and Biophys.Res. Comm. 77 , 581-585, (1977)] have been reported. When the anhydrides are coupled to proteins the coupling proceeds via formation of an amide bond thus leaving four of the original five carboxymethyl groups on the diethylenetriamine (DETA) backbone [Hnatowich et al. Int.J. Appl. Isot. 33 , 327-332, (1982)]. In addition, U.S. Patents 4,432,907 and 4,352,751 disclose bifunctional chelating agents useful for binding metal ions to "organic species such as organic target molecules or antibodies." As in the above, coupling is obtained via an amide group through the utilization of diaminotetraacetic acid dianhydrides. Examples of anhydrides include dianhydrides of EDTA, CDTA, propylenediaminetetraacetic acid and phenylene 1,2-diaminetetraacetic acid. A recent U.S. Patent 4,647,447 discloses several complex salts formed from the anion of a complexing acid for use in various diagnostic techniques. Conjugation via a carboxyl group of the complexing acid is taught which gives a linkage through an amide bond. In the J. of Radioanalytical Chemistry 57 (12), 553-564 (1980), Paik et al. disclose the use of p-nitrobenzylbromide in a reaction with a "blocked" diethylenetriamine, i.e. bis-(2-phthalimidoethyl)amine followed by deblocking procedures and carboxymethylation using chloroacetic acid, to give N′-p-nitrobenzyldiethylenetriamine N,N,N″,N″-tetraacetic acid. Again, since the attachment is through a nitrogen, a tetraacetic acid derivative is obtained. Conjugation of the bifunctional chelating agent and chelation with indium is discussed. Substitution on the nitrogen atom is also taught by Eckelman, et al. in the J. of Pharm. Sci. 64 (4), 704-706 (1975) by reacting amines such as "ethylenediamine or diethylenetriamine with the appropriate alkyl bromide before carboxymethylation." The compounds are proposed as potential radiopharmaceutical imaging agents. Another class of bifunctional chelating agents based on aminocarboxylic acid functionality is also well documented in the literature. Thus, Sundberg, Meares, et al. in the J. of Med. Chem. 17 (12), 1304 (1974), disclosed bifunctional analogs of EDTA. Representative of these compounds are 1-(p-aminophenyl)-ethylenediaminetetraacetic acid and 1-(p-benzene-diazonium)-ethylenediaminetetraacetic acid. Coupling to proteins through the para-substituent and the binding of radioactive metal ions to the chelating group is discussed. The compounds are also disclosed in Biochemical and Biophysical Research Communications 75 (1), 149 (1977), and in U.S. Patents 3,994,966 and 4,043,998. It is important to note that the attachment of the aromatic group to the EDTA structure is through a carbon of the ethylenediamine backbone. Optically active bifunctional chelating agents based on EDTA, HEDTA and DTPA are disclosed in U.S. 4,622,420. In these compounds an alkylene group links the aromatic group (which contains the functionality needed for attachment to the protein) to the carbon of the polyamine which contains the chelating functionality. Other references to such compounds include Brechbiel et al., Inorg. Chem. 25, 2772-2781 (1986), U.S. Patent 4,647,447 and International Patent Publication No. WO 86/06384. More recently, certain macrocyclic bifunctional chelating agents and the use of their copper chelate conjugates for diagnostic or therapeutic applications have been disclosed in U.S. Patent 4,678,667 and by Moi et al., Inorg. Chem. 26, 3458-3463 (1987). Attachment of the aminocarboxylic acid functionality to the rest of the bifunctional chelating molecule is through a ring carbon of the cyclic polyamine backbone. Thus, a linker, attached at one end to a ring carbon of the cyclic polyamine, is also attached at its other end to a functional group capable of reacting with the protein. Another class of bifunctional chelating agents, also worthy of note, consists of compounds wherein the chelating moiety, i.e. the aminocarboxylic acid, of the molecule is attached through a nitrogen to the functional group of the molecule containing the moiety capable of reacting with the protein. As an example, Mikola et al. in patent application (International Publication Number WO 84/03698, published 9/27/1984) disclose a bifunctional chelating agent prepared by reacting p-nitrobenzylbromide with DETA followed by reaction with bromoacetic acid to make the aminocarboxylic acid. The nitro group is reduced to the corresponding amine group and is then converted to the isothiocyanate group by reaction with thiophosgene. These compounds are bifunctional chelating agents capable of chelating lanthanides which can be conjugated to bio-organic molecules for use as diagnostic agents. Since attachment of the linker portion of the molecule is through one of the nitrogens of the aminocarboxylic acid, then one potential aminocarboxyl group is lost for chelation. Thus, a DETA-based bifunctional chelant containing four (not five) acid groups is prepared. In this respect, this class of bifunctional chelant is similar to those where attachment to the protein is through an amide group with subsequent loss of a carboxyl chelating group. Recently Carney, Rogers, and Johnson disclosed (3rd. International Conference on Monoclonal Antibodies For Cancer; San Diego, California - 2/4-6/88) abstracts entitled "Absence of Intrinsically Higher Tissue Uptake from Indium-111 Labeled Antibodies: Co-administration of Indium-111 and Iodine-125 Labeled B72.3 in a Nude Mouse Model" and "Influence of Chelator Denticity on the Biodistribution of Indium-111 Labeled B72.3 Immunoconjugates in Nude Mice". The biodistribution of indium-111 complexed with an EDTA and DTPA bifunctional chelating agent is disclosed. Attachment of the aromatic ring to the EDTA/DTPA moieties is through an acetate methylene. Also at a recent meeting D.K. Johnson et al. [Florida Conf. on Chem. in Biotechnology, April 26-29 (1988), Palm Coast, FL] disclosed bifunctional derivatives of EDTA and DTPA where a p-isothiocyanatobenzyl moiety is attached at the methylene carbon of one of the carboxymethyl groups. Previously Hunt et al. in U.S. Patents 4,088,747 and 4,091,088 (1978) disclosed ethylenediaminediacetic acid (EDDA) based chelating agents wherein attachment of an aromatic ring to the EDDA moiety is through the alkylene or acetate methylene. The compounds are taught to be useful as chelates for studying hepatobiliary function. The preferred metal is technetium-99m. Indium-111 and indium-113m are also taught as useful radionuclides for imaging. EP-A-0 292 689, published on November 30, 1988, discloses substituted 1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecanes and analogues, complexes thereof with rare earth metal ions and their use in the radiotherapy. EP-A-0 296 522, published on December 28, 1988, discloses functionalized polyamine chelants, which form complexes with rhodium. The rhodium complexes can be bound to an antibody or to an antibody fragment and can be employed for therapeutical or diagnostic purposes. EP-A-0 232 751, published on August 19, 1987, discloses tris-carboxymethyl tetraazadodecane derivatives, wherein the fourth nitrogen substitute contains an aryl-alkyl group, if necessary. The term "aryl" according to EP-A-0 232 751 refers to phenyl and substituted phenyl. Preferred substituted phenyl groups are those substituted with one, two or three halogens, hydroxyl, alkyl, alkoxy, carbamoyl or carboxyl groups. The positions of these substituents is however not disclosed. Consequently, it would be advantageous to provide a complex that does not readily dissociate, that exhibits rapid whole body clearance except from the desired tissue, and conjugates with an antibody to produce the desired results. Brief Description of the Drawings Figures 1-7 and 15-21 show the biodistribution of ¹⁵³Sm as administered as a conjugate containing ¹⁵³Sm of the present invention. The antibody, CC₄₉-IgG, was used in the conjugate of the present invention. The biodistribution was determined in nude mice bearing LS 174-T tumor. Figures 8-14 and 22-28 show the biodistribution of ¹⁵³Sm as administered as a conjugate containing ¹⁵³Sm of the present invention. The conjugate of the present invention used CC₄₉-F(ab′)₂ as the antibody fragment . The biodistribution was determined in nude mice bearing LS 174-T tumor. Figures 29-34 show the biodistribution of ¹⁷⁷Lu as a conjugate containing ¹⁷⁷Lu(PA-DOTMA). The conjugate used CC₄₉-IgG as the antibody. The biodistribution was determined in nude mice (blab/C) bearing LS 174-T tumor. Surprisingly, the complexes and/or conjugates of the invention are relatively stable (i.e. do not easily dissociate) and some display rapid clearance from the whole body except from the desired tissue. The invention includes the design and synthesis of novel bifunctional chelants, each containing a chelating functionality, and a chemically reactive group for covalent attachment to biomolecules. Also forming part of the invention are methods for preparing various bifunctional coordinator (BFC)-metal complexes and the linking of the complexes to antibody to prepare radionuclide (such as samarium-153, lutetium-177 and yttrium-90) labeled antibody and/or fragments suitable for diagnostic and/or therapeutic applications. The present invention is directed to novel bifunctional chelating agents that form complexes with metal ions, especially "radioactive" metal ions having rare earth-type chemistry. Preferred rare earth-type metal ions include La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y and Sc. Preferred radioactive rare earth-type metal ions include ¹⁵³Sm, ¹⁶⁶Ho, ⁹⁰Y, ¹⁴⁹Pm, ¹⁵⁹Gd, ¹⁴⁰La, ¹⁷⁷Lu, ¹⁷⁵Yb, ⁴⁷Sc, and ¹⁴²Pr. Other radioactive metal ions which may be of interest are ⁴⁷Sc, 99m Tc, ¹⁸⁶Re, ¹⁸⁸Re, ⁹⁷Ru, ¹⁰⁵Rh, ¹⁰⁹Pd, ¹⁹⁷Pt, ⁶⁷Cu, ¹⁹⁸Au, ¹⁹⁹Au, ⁶⁷Ga, ⁶⁸Ga, ¹¹¹In, 113m In, 115m In, 117m Sn, and ²¹²Pb/²¹²Bi. The complexes so formed can be attached (covalently bonded) to an antibody or fragment thereof and used for therapeutic and/or diagnostic purposes. The complexes and/or conjugates can be formulated for in vivo or in vitro uses. A preferred use of the formulated conjugates is the treatment of cancer in animals, especially humans. Uses of the complexes and/or conjugates of this invention which contain a non-radioactive metal for diagnosis and/or treatment of disease states such as cancer are also possible. Such uses are known for non-radioactive metals using radio frequency to induce hyperthermia (Jpn. Kokai Tokkyo Koho JP 61,158,931) and fluorescent-immunoguided therapy (FIGS) [K. Pettersson et al., Clinical Chemistry 29 (1), 60-64 (1983) and C. Meares et al., Acc . Chem . Res . 17 , 202-209 (1984]. A subject-matter of the present invention is a compound of the formula: wherein: each Q is independently hydrogen or (CHR⁵ ) p CO₂R; Q¹ is hydrogen or (CHR⁵ ) w CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least two of the sum of Q and Q¹ must be other than hydrogen, and that when Q¹ is hydrogen, R³ must be other than hydrogen; each R⁵ independently is hydrogen or C₁-C₄ alkyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p = 1 or 2; r = 0 or 1; w = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond, and the sun of r and w is 0 or 1; R² is hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromacetamido or carboxyl; R³ is C₁-C₄ alkoxy, -OCH₂CO₂H, hydroxy or hydrogen; R⁴ is hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; with the proviso that R² and R⁴ cannot both be hydrogen but one of R² and R⁴ must be hydrogen; or a pharmaceutically acceptable salt thereof. Preferred compounds of formula (IA) are subject-matter of claims 2-35. Preferred features of the compounds of formula (IA) are those where: R is hydrogen; R⁵ is H or methyl; n is 0; m is 0 through 5; r is 0. A further subject-matter of the present invention is a complex comprising a compound as defined above or a pharmaceutically acceptable salt thereof, complexed with an ion of a metal selected from La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y and Sc. Preferred complexes of the present invention are subject-matter of the claims 37-60. Yet another subject-matter of the present invention is a conjugate comprising a complex as defined above with the proviso that R² and R⁴ cannot be nitro, and covalently attached to an antibody or antibody fragment. Preferred conjugates are subject-matter of the claims 62-70. Yet a further subject-matter of the present invention is a conjugate comprising a compound as defined above or a pharmaceutically acceptable salt thereof, covalently attached to an antibody or antibody fragment. Preferred conjugates are subject matter of the claims 72-75. Yet a further subject-matter of the present invention is a process for preparing a compound as defined above according to claim 76. Still a further subject-matter of the present invention is a process for preparing a mono-N-alkylated-polyazamacrocycle according to claims 77 and 78. When a conjugate of the present invention is desired R² and R⁴ must be other than nitro. When R² or R⁴ is nitro, then a precursor of the linker moiety (L) is present This precursor moiety can be any moiety which is formed for R² or R⁴ for the preparation of the compounds of formula (I) and which does not bind to an antibody or antibody fragment. The present invention is also directed to rare-earth type metal ion complexes, especially radioactive neutral or charged rare-earth type metal ion complexes, and to conjugates formed with the aforementioned complexes and antibody or antibody fragments. In addition the present invention also includes formulations having the conjugates of the invention and a pharmaceutically acceptable carrier, especially formulations where the pharmaceutically acceptable carrier is a liquid. The invention also includes a method for the diagnosis or treatment of a disease state, especially cancer, in a mammal which comprises administering to the mammal an effective amount of the formulation. Detailed Description of the Invention As used herein, the following indicated terms have these meanings: with respect to the definition of R¹, R² or R⁴, "electrophilic" moieties include, but are not limited to, isothiocyanate, bromoacetamide, maleimide, imidoester, thiophthalimide, N-hydroxysuccinimyl ester, pyridyl disulfide, and phenyl azide; suitable "nucleophilic" moieties include, but are not limited to, carboxyl, amino, acyl hydrazide, semicarbazide, and thiosemicarbazide; "synthetic linkers" include any synthetic organic or inorganic linkers which are capable of being covalently attached to an antibody or antibody fragment, preferred synthetic linkers are biodegradable synthetic linkers which are stable in the serum of a patient but which have a potential for cleavage within an organ of clearance for the radioisotope, for example biodegradable peptides or peptide containing groups. Of the electrophilic moieties isothiocyanate is preferred and of the nucleophilic moieties amino, semicarbazide and thiosemicarbazide are preferred. It is desirable that the nature and/or position of R¹ be such that it does not appreciably interfere with the chelation reaction. The "X-C-Y" term in formula (I) represents the optional presence of a double or triple bond between adjacent carbon atoms. The unsaturated bonds may be present independently in the chain length of 0 to 10 carbon atoms inclusive as defined by the "m" term in formula (I). As used herein, the term "mammal" means animals that nourish their young with milk secreted by mammary glands, preferably warm blooded mammals, more preferably humans. "Antibody" refers to any polyclonal, monoclonal, chimeric antibody or heteroantibody, preferably a monoclonal antibody; "antibody fragment" includes Fab fragments and F(ab′)₂ fragments, and any portion of an antibody having specificity toward a desired epitope or epitopes. When using the term "metal chelate/antibody conjugate" or "conjugate", the "antibody" portion is meant to include whole antibodies and/or antibody fragments, including semisynthetic or genetically engineered variants thereof. As used herein, "complex" refers to a compound of the invention, e.g. formula (I), complexed with a rare-earth type metal ion, especially a radioactive rare-earth type metal ion, wherein at least one metal atom is chelated or sequestered; "radioactive metal ion chelate/antibody conjugate" or "radioactive metal ion conjugate" refers to a radioactive metal ion conjugate that is covalently attached to an antibody or antibody fragment; "radioactive" when used in conjunction with the word "metal ion" refers to one or more isotopes of the rare-earth type elements that emit particles and/or photons, such as ¹⁵³Sm, ¹⁶⁶Ho, ⁹⁰Y, ¹⁴⁹Pm, ¹⁵⁸Gd, ¹⁴⁰La, ¹⁷⁷Lu, ¹⁷⁵Yb, ⁴⁷Sc, and ¹⁴²Pr; the terms "bifunctional coordinator", "bifunctional chelating agent" and "functionalized chelant" are used interchangeably and refer to compounds that have a chelant moiety capable of chelating a metal ion and a linker/spacer moiety covalently bonded to the chelant moiety that is capable of serving as a means to covalently attach to an antibody or antibody fragment. As used herein, "pharmaceutically acceptable salt" means any salt of a compound of formula (I) which is sufficiently non-toxic to be useful in therapy or diagnosis of mammals. Thus, the salts are useful in accordance with this invention. Representative of those salts, which are formed by standard reactions, from both organic and inorganic sources include, for example, sulfuric, hydrochloric, phosphoric, acetic, succinic, citric, lactic, maleic, fumaric, palmitic, cholic, palmoic, mucic, glutamic, d -camphoric, glutaric, glycolic, phthalic, tartaric, formic, lauric, steric, salicylic, methanesulfonic, benzenesulfonic, sorbic, picric, benzoic, cinnamic acids and other suitable acids. Also included are salts formed by standard reactions from both organic and inorganic sources such as ammonium, alkali metal ions, alkaline earth metal ions, and other similar ions. Particularly preferred are the salts of the compounds of formula (I) where the salt is potassium, sodium, ammonium, or mixtures thereof. Of course, the free acid of the compounds of formula (I) may be used, also the protonated form of the compounds, for example when the carboxylate is protonated and/or the nitrogen atoms i.e. when the HCl salt is formed. Preferred compounds of formula (I) include those compounds where Q¹ is hydrogen and L is represented by formula A as shown by the following formula: wherein: each Q is independently hydrogen or CHR⁵CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least two of Q must be other than hydrogen; m is an integer from 0 to 5 inclusive; R² is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, bromoacetamido and maleimido; R³ is selected from the group consisting of C₁-C₄ alkoxy, -OCH₂CO₂H, hydroxy and hydrogen; R⁴ is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, bromoacetamido and maleimido; each R⁵ independently is hydrogen or C₁-C₄ alkyl; with the proviso that R² and R⁴ cannot both be hydrogen but one of R² and R⁴ must be hydrogen; or a pharmaceutically acceptable salt thereof. In formula (II) when R³ and R⁴ are both hydrogen, the compounds are represented by the following formula: wherein: each Q is independently hydrogen or CHR⁵CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least two of Q must be other than hydrogen; m is an integer from 0 to 5 inclusive; R² is selected from the group consisting of nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, bromoacetamido and maleimido; each R⁵ independently is hydrogen or C₁-C₄ alkyl; or a pharmaceutically acceptable salt thereof. In formula (II) when R² is hydrogen, the compounds are represented by the formula: wherein: each Q is independently hydrogen or CHR⁵CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least two of Q must be other than hydrogen; m is an integer from 0 to 5 inclusive; R³ is selected from the group consisting of C₁-C₄ alkoxy, -OCH₂CO₂H and hydroxy; R⁴ is selected from the group consisting of nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, bromoacetamido, and maleimido; each R⁵ independently is hydrogen or C₁-C₄ alkyl; or a pharmaceutically acceptable salt thereof. Additional preferred compounds of formula (I) include those compounds where at least one Q is hydrogen and are represented by the formula: wherein: each Q is independently hydrogen or CHR⁵CO₂R; Q¹ is hydrogen or (CHR⁵) w CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least two of the sum of Q and Q¹ must be other than hydrogen and one of Q is hydrogen; m is an integer from 0 to 5 inclusive; w is 0 or 1; R² is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, maleimido and bromoacetamido; R³ is selected from the group consisting of C₁-C₄ alkoxy, -OCH₂CO₂H, hydroxy and hydrogen; R⁴ is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, maleimido and bromoacetamido; each R⁵ independently is hydrogen or C₁-C₄ alkyl; with the proviso that R² and R⁴ cannot both be hydrogen but one of R² and R⁴ must be hydrogen; or a pharmaceutically acceptable salt thereof. Other preferred compounds of formula (I) include compounds where Q¹ is CO₂R (w=o) and are represented by the formula: wherein: each Q is independently hydrogen or CHR⁵CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least one Q must be other than hydrogen; m is an integer from 0 to 5 inclusive; R² is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, maleimido and bromoacetamido; R³ is selected from the group consisting of C₁-C₄ alkoxy, -OCH₂CO₂H, hydroxy and hydrogen; R⁴ is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, maleimido and bromoacetamido; each R⁵ independently is hydrogen or C₁-C₄ alkyl; with the proviso that R² and R⁴ cannot both be hydrogen but one of R² and R⁴ must be hydrogen; or a pharmaceutically acceptable salt thereof. Some preferred compounds of formula (VI) are those where R³ and R⁴ are both hydrogen, the compounds are represented by the formula: wherein: each Q is independently hydrogen or CHR⁵CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least one Q must be other than hydrogen; m is an integer from 0 to 5 inclusive; R² is selected from the group consisting of nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, bromoacetamido and maleimido; each R⁵ independently is hydrogen or C₁-C₄ alkyl; or a pharmaceutically acceptable salt thereof. Other preferred compounds of formula (VI) are those where R² is hydrogen and are represented by the formula: wherein: each Q is independently hydrogen or CHR⁵CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least one Q must be other than hydrogen; m is an integer from 0 to 5 inclusive; R³ is selected from the group consisting of C₁-C₄ alkoxy, -OCH₂CO₂H, and hydroxy; R⁴ is selected from the group consisting of nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, carboxyl, maleimido, and bromoacetamido; each R⁵ independently is hydrogen or C₁-C₄ alkyl; or a pharmaceutically acceptable salt thereof. The bifunctional chelating agents described herein [represented by any one of formulas (I)-(VIII)] can be used to chelate or sequester the rare-earth type metal ions, particularly radioactive rare-earth type metal ions, so as to form metal ion chelates (also referred to herein as "complexes"). The complexes, because of the presence of the functionalizing moiety [represented by "R¹" in formula (I)], can be attached to functionalized supports, such as functionalized polymeric supports, or preferably, when a complex of formula (I) where L represents formula (A) and R² and R⁴ must be other than nitro, can be covalently attached to proteins or more specifically to antibodies or antibody fragments. Thus the complexes described herein (represented by any one of formulas I-VIII complexed with rare-earth type metal ions, particularly radioactiye rare-earth type metal ions) may be covalently attached to an antibody or antibody fragment and are referred to herein as "conjugates". The antibodies or antibody fragments which may be used in the conjugates described herein can be prepared by techniques well known in the art. Highly specific monoclonal antibodies can be produced by hybridization techniques well known in the art, see for example, Kohler and Milstein [ Nature 256 , 495-497 (1975); and Eur. J. Immunol . 6 , 511-519 (1976)]. Such antibodies normally have a highly specific reactivity. In the radioactive metal ion conjugates, antibodies directed against any desired antigen or hapten may be used. Preferably the antibodies which are used in the radioactive metal ion conjugates are monoclonal antibodies, or fragments thereof having high specificity for a desired epitope(s). Antibodies used in the present invention may be directed against, for example, tumors, bacteria, fungi, viruses, parasites, mycoplasma, differentiation and other cell membrane antigens, pathogen surface antigens, toxins, enzymes, allergens, drugs and any biologically active molecules. Some examples of antibodies or antibody fragments are CC-11, CC-46, CC-49, CC-49 F(ab')₂, CC-83, CC-83 F(ab')₂, and B72.3. [See D. Colcher et al., Cancer Res . 48 , 4597-4603 (Aug. 15, 1988) for CC-49, CC-83 and B72.3 antibodies. The hybridoma cell line B72.3 is deposited in the American Type Culture Collection (ATCC) having the accession number HB 8108. The various CC antibodies are disclosed in United States patent application 7-073,685, filed July 15, 1987, which is available through NTIS. The other murine monoclonal antibodies bind to epitopes of TAG-72, a tumor associated antigen.] A more complete list of antigens can be found in U.S. Patent 4,193,983. The radioactive metal ion conjugates of the present invention are particularly preferred for the diagnosis and treatment of various cancers. The preferred rare-earth type (lanthanide or pseudo-lanthanide) complexes of the present invention are represented by the formula: C[Ln(BFC)] (IX) wherein: Ln is a rare-earth metal (lanthanide) ion, such as Ce³⁺, Pr³⁺, Nd³⁺, Pm³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Dy³⁺, Ho³⁺, Er³⁺, Tm³⁺, Yb³⁺ and Lu³⁺, or pseudo-lanthanide metal ion, such as Sc³⁺, Y³⁺ and La³⁺; BFC represents a bifunctional chelant; and C represents a pharmaceutically acceptable ion or group of ions of sufficient charge to render the entire complex neutral. If the BFC contains four or more negatively charged moieties, then C is a cation or group of cations such as H⁺, Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺, Mg²⁺, Ca²⁺, Sr²⁺, Ba²⁺, NH4⁺, N(CH₃)₄⁺, N(C₂H₅)₄⁺, N(C₃H₇)₄⁺, N(C₄H₉)₄⁺, As(C₆H₅)₄⁺, [(C₆H₅)₃P=]₂N⁺ and other protonated amines. If the BFC contains three negatively charged moieties, then C is not required. If the BFC contains two negatively charged moieties, then C is an anion such as F⁻, Cl⁻, Br⁻, I⁻, ClO₄⁻, BF₄⁻, H₂PO₄⁻, HCO₃⁻, HCO₂⁻, CH₃SO₃⁻, H₃C-C₆H₄-SO₃⁻, PF₆⁻, CH₃CO₂⁻ and B(C₆H₅)₄⁻. The conjugates of this invention, and in some instances the complexes of this invention, may be employed as a formulation. The formulation comprises a compound of formula (I) with the antibody and/or metal ion and a physiologically acceptable carrier, excipient or vehicle therefore. Thus, the formulation may consist of a physiologically acceptable carrier with a complex (metal ion + ligand), conguate (metal ion + ligand + antibody) or (ligand + antibody). The methods for preparing such formulations are well known. The formulation may be in the form of a suspension, injectable solution or other suitable formulation. Physiologically acceptable suspending media, with or without adjuvants, may be used. The formulations of the present invention are in the solid or liquid form containing the active radionuclide complexed with the ligand. These formulations may be in kit form such that the two components (i.e. ligand and metal, complex and antibody, or ligand/antibody and metal) are mixed at the appropriate time prior to use. Whether premixed or as a kit, the formulations usually require a pharmaceutically acceptable carrier. Injectable compositions of the present invention may be either in suspension or solution form. In the preparation of suitable formulations it will be recognized that, in general, the water solubility of the salt is greater than the acid form. In solution form the complex (or when desired the separate components) is dissolved in a physiologically acceptable carrier. Such carriers comprise a suitable solvent, preservatives such as benzyl alcohol, if needed, and buffers. Useful solvents include, for example, water, aqueous alcohols, glycols, and phosphonate or carbonate esters. Such aqueous solutions contain no more than 50 percent of the organic solvent by volume. Injectable suspensions are compositions of the present invention that require a liquid suspending medium, with or without adjuvants, as a carrier. The suspending medium can be, for example, aqueous polyvinylpyrrolidone, inert oils such as vegetable oils or highly refined mineral oils, or aqueous carboxymethylcellulose. Suitable physiologically acceptable adjuvants, if necessary to keep the complex in suspension, may be chosen from among thickners such as carboxymethylcellulose, polyvinylpyrrolidone, gelatin, and the alginates. Many surfactants are also useful as suspending agents, for example, lecithin, alkylphenol, polyethylene oxide adducts, napthalenesulfonates, alkylbenzenesulfonates, and the polyoxyethylene sorbitan esters. Many substances which effect the hydrophilicity, density, and surface tension of the liquid suspension medium can assist in making injectable suspensions in individual cases. For example, silicone antifoames, sorbitol, and sugars are all useful suspending agents. An "effective amount" of the formulation is used for therapy. The dose will vary depending on the disease being treated. Although in vitro diagnostics can be performed with the formulations of this invention, in vivo diagnostics are also contemplated using formulations of this invention. The conjugates and formulations of this invention can also be used in radioimmuno guided surgery (RIGS); however, other metals which could be used for this purpose also include 99m Tc, ¹¹¹In, 113m In, ⁶⁷Ga and ⁶⁸Ga. Other uses of some of the chelants of the present invention may include magnetic resonance imaging, e.g. the complexes of formula I, especially complexes of formula VI, with Gd⁺³, attachment to polymeric supports for various purposes, e.g. as diagnostic agents, and removal of lanthanide metal or pseudo-lanthanide metal ion by selective extraction. The present invention provides chelants, complexes, and antibody conjugates some of which are more stable, and/or have improved biodistribution, and/or have more rapid clearance from the body, than those known in the art. Detailed Description of the Process A reasonable and general synthetic approach to a twelve-membered macrocyclic, bifunctional chelant of the present invention as represented by formula (I) involves monofunctionalization of a free-base macrocycle (e.g. 1,4,7,10-tetraazacyclododecane) at only one of the nitrogen atoms with an appropriate electrophile (eg. any appropriately substituted α-halocarboxylic acid ester). This electrophile must possess a suitable linker moiety or suitably protected linker moiety which would allow covalent attachment of the bifunctional ligand to a protein, antibody or antibody fragment. It is recognized in the art that alkylative techniques for the production of mono-N-functional polyazamacrocycles may result in mixtures of difficult to separate products [T. Kaden, Top . Curr . Chem . 121 , 157-75 (1984)]. This problem has been overcome through the reported use of large excesses of macrocycle (5-10 equivalents relative to electrophile) which favors formation of the monoalkylation adduct [M. Studer and T.A. Kaden, Helv.Chim.Acta 69 , 2081-86 (1986); E. Kimura et al., J.Chem.Soc.Chem.Commun. 1158-59 (1986)]. Other routes to mono-N-functional polyazamacrocycles involve lengthy protection, functionalization, and deprotection schemes [P. S. Pallavicini et al., J.Amer . Chem.Soc . 109, 5139-44 (1987); M. F. Tweedle et al., Eur . Pub.Pat.Appln.No . 0232-751]. A recent report of a reductive amination of substituted phenyl pyruvic acids and amines has issued by Abbott Labs. as an Abstract from a recent meeting (D. K. Johnson et al., Florida Conf. on Chem. in Biotechnology, April 26-29 (1988), Palm Coast, FL). A process that prepares mono-N-alkylated polyazamacrocycles by using an electrophile with between about one and five equivalents of a suitable macrocycle in a solvent which will not promote a proton transfer is disclosed in EP-A-0 374 929, Published on June 27, 1990. General synthetic routes to the chelants of the present invention are disclosed in Synthesis Schemes I-IV hereinafter and involve the reaction of a suitable electrophile and the polyazamacrocycle in an appropriate organic solvent. Examples of suitable organic solvents are any hydrocarbon which supports solubility, such as acetonitrile, isopropanol, methylene chloride, toluene, chloroform, n-butanol, carbon tetrachloride, tetrahydrofuran, 5% ethanol in chloroform, with the most preferred being chloroform, methylene chloride, n-butanol, 1,4-dioxane and acetonitrile. Various stoichiometric amounts of reactants, temperatures and concentrations can be used. Nearly stoichiometric amounts of macrocycle and electrophile may be employed and yield the corresponding mono-N-alkylation product in a single step. The temperature range for the reaction is from about 0°C to about reflux, preferably from 0°C to 25°C. The time of the reaction is until completion about 1 to about 24 hours. General access to substituted α-haloacid esters is desirable for the overall viability of Synthesis Schemes II and IV. One suitable approach involves bromination or chlorination of the acid halide generated in situ , e.g. D.N. Harpp et al., J. Org. Chem. 40, 3420-27 (1975). This approach allows for exclusive alpha halogenation of alkanoic acids which contain even reactive benzylic groups. A general method to substituted acid halides involves reaction of the organic acid with thionyl chloride or sulfuryl chloride, e.g. E. Schwenk et al. J. Amer. Chem. Soc. 70 , 3626-27 (1944). Both methods utilize the free carboxylic acid which is frequently available from commercial sources. Polyazamacrocycles such as 1,4,7,10-tetraazacyclododecane may be prepared by documented methods such as T.J. Atkins et al., J. Amer. Chem. Soc. 96 , 2268-70 (1974) and T.J. Richman et al., Org. Synthesis 58 , 86-98 (1978). Carboxymethylation of the mono-N-functional macrocycle may be performed by the method of Desreux using bromoacetic acid derivatives and a suitable base [J.F. Desreux, Inorg. Chem. 19 , 1319-24 (1980)]. All of the starting materials required for preparing the compounds of this invention are either available from commercial sources or can be made from a known literature reference descriptions. In the following Scheme I, the compounds of formula (I) are prepared where Q¹ is hydrogen. Although only one compound is indicated by the terms shown, other similar moieties within formula (I) where Q¹ is hydrogen, r = 0 or 1, n = 0 or 1, and m = 0 through 10 can also be prepared by this method. In the following Scheme II, the compounds of formula (I) are prepared where Q¹ is hydrogen. Although only one compound is indicated by the terms shown, other similar moieties within formula (I) where Q¹ is hydrogen, r = 0 or 1, n = 0 or 1 and m = 0 through 10 can also be prepared by this method. In the following Scheme III, the compounds of formula (I) are prepared where Q¹ is CO₂R. Although only one compound is indicated by the terms shown, other similar moieties within formula (I) where Q¹ is CO₂R, including m=0 through 10, n=0 or 1 and r = 0 can also be prepared by this method. In the following Scheme IV, the compounds of formula (I) are prepared where Q¹ is (CHR⁵) w CO₂R. Although only one compound is indicated by the terms shown, other similar moieties within formula (I) where Q¹ is (CHR⁵) w CO₂R, including m=0 through 10, n=0 or 1 and r = 0 can also be prepared by this method. Use of an optically active alkylating agent has minimized the diastereomers and simplifies the synthesis. Isolation of a single diastereomer which would give rise to a single, easily purified lanthanide complex would be desirable for radiochelation as well as antibody conjugation. In the following Scheme V, the compounds of formula (I) are prepared where Q¹ is hydrogen or (CHR⁵) w CO₂R and R² is hydrogen. Although only two compounds are indicated by the terms shown, other similar moieties within formula (I) where Q¹ is hydrogen or (CHR⁵) w CO₂R, Q is hydrogen or (CHR⁵) p CO₂R, r = 0 or 1, n = 0 or 1, w = 0 or 1, m = 0 through 10, p = 1 or 2, L represents formula A wherein R³ is defined as before, R² and R⁴ are selected from the group consisting of hydrogen, amino, nitro, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl, can also be prepared by this method. The electrophilic moiety ("R¹" in the formula) can also be prepared by methods known to the art. Such methods may be found in Acc.Chem.Res. 17 , 202-209 (1984). A process that can prepare compounds of formula (I) where R¹ could be an isothiocyanato moiety (R² or R⁴ present are isothiocyanato when L = formula A) involves reacting the amino chelate (R² or R⁴ equal amino, present when L = formula A) with thiophosgene and is disclosed in EP-A-0 374 947, published on June 27, 1990. Radionuclides can be produced in several ways. In a nuclear reactor a nuclide is bombarded with neutrons to obtain a radionuclide, e.g. Sm-152 + neutron → Sm-153 + gamma Another method of obtaining radionuclides is to bombard nuclides with particles in a linear accelerator or a cyclotron. Yet another way is to isolate the radionuclide from a mixture of fission products. The method of obtaining the nuclides employed in the present invention is not critical thereto. The conjugates of the present invention can be prepared by first forming the complex and then binding the antibody or antibody fragment. Thus the process involves preparing or obtaining the ligand, forming the complex with the metal and then adding the antibody. Alternatively, a process for making labeled antibody conjugates can involve first conjugation of the BFC to the antibody and its subsequent chelation to yield the radionuclide-BFC labeled Ab. Any suitable process that results in the formation of the conjugates of this invention is within the scope of this invention. In the following examples, the following terms and conditions were used unless otherwise specified. General Experimental Mass spectra were obtained on either a Finnigan TSQ mass spectrometer (Q¹MS mode) or a VG ZAB-MS high resolution mass spectrometer (fast atom bombardment with xenon, using 3:1 dithiothreitol:dithioerythritol). ¹H and ¹³C NMR spectra were obtained using a Varian VXR-300, Bruker APC 300, IBM/Bruker NR-80 or a Jeol FX400 spectrometer. All spectra were obtained at 30°C unless otherwise noted. ¹H NMR was done at 300 MHz, 80 MHz or 400 MHz, respectively to the equipment listed above; ¹³C NMR was done at 75 MHz, 20 MHz or 100 MHz, respectively to the equipment listed above. The values for the NMR are δ versus TMS (tetramethylsilane) or when D₂O was the solvent versus DSS (2,2-dimethyl-2-silapentane-5-sulfonic acid, sodium salt). Infrared spectra (IR) were recorded on a Nicolet 5SX FT/IR instrument. For the chromatography procedures, most solvents were Fisher HPLC grade materials. Ammonium acetate was purchased from Aldrich. Water was purified using a Barnstead NANOpure™ water filtration system. Preparative chromatography of organic compounds was performed either by normal gravity chromatography using standard techniques or by flash chromatography as described by C.W. Still et al., J. Org. Chem. 43 , 2923-24 (1978). The following solvent systems were used: Solvent System Components 1 CHCl₃:CH₃OH:conc. NH₄OH 2:2:1 V:V:V 2 CHCl₃:CH₃OH:conc. NH₄OH 12:4:1 V:V:V 3 CHCl₃:CH₃OH:conc. NH₄OH 16:4:1 V:V:V 4 CHCl₃:CH₃OH:conc. NH₄OH 4:2:1 V:V:V 5 CHCl₃:CH₃OH:conc. NH₄OH 3:2:1 V:V:V 6 CHCl₃:CH₃OH:conc. NH₄OH 7:3:1 V:V:V 7 saline (0.85% of NaCl in distilled water):conc. NH₄OH 4:1 V:V 8 CHCl₃:CH₃OH:conc. NH₄OH 4:4:1 V:V:V R f values are reported using these solvent systems and commercially available, normal phase, silica TLC plates [GHLF 250 micron, Analtech Inc. or Merck Kiesel gel 60F₂₅₄] Preparative column chromatography was done using Merck grade 60, 60 Å silica gel. All percentages are by weight unless stated otherwise. Some solids were dried using a rotary evaporator (Buchi 461) and/or a vacuum oven at a temperature of about 55-60°C for several hours. In addition, a Virtis model 10-010 automatic freezer dryer or Speed Vac™ concentrator was used for solvent removal. Samarium-153 and lutetium-177 were produced by the Research Reactor, University of Missouri (Columbia, MO). Yttrium-90 was purchased from Oak Ridge National Laboratory. 1-(4-Isothiocyanatobenzyl)diethylenetriaminepentaacetic acid (SCN-Bz-DTPA) was prepared by a modification to the procedure of M. W. Brechbiel, et al., Inorg. Chem. 25 , 2772-2781 (1986), and purified to give a single species on anion exchange HPLC (Q-Sepharose™). Some of the chemicals used were obtained from the sources indicated: N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES), free acid and sodium salt were purchased from Behring Diagnostics (La Jolla, CA); sodium citrate (certified) was from Fisher Scientific; thiophosgene was from Aldrich Chemicals; ammonium acetate, sodium acetate, ethylenediaminetetraacetic acid (EDTA) and phosphate buffered saline (PBS) were from Sigma Diagnostics. HPLC columns used were: Hand-packed Q-Sepharose™ (Pharmacia) either 1.5 cm x 25 cm or 2.5 cm x 25 cm; Zorbax™ BIO Series GF-250 (9.4 mm x 25 cm) from Du Pont Instruments; Vydac™ (Trademark of the Separations Group, Hesperia, CA) protein C-4 (4.6 mm x 25 cm) from the Separation Group (Hesperia, CA); and Mono-Q™ and SP-Sephadex™ (Tradename of Pharmacia Biotechnology Products) from Pharmacia. Sep-Pak™ (Tradename of Waters Associates) C-18 cartridge was purchased from Waters Associates (Milford, MA), Sephadex™ G-25 disposable columns (2.2 ml) from Isolab Inc. (Akron, OH), and Centricon™-30 (Tradename of Amicon Division, W. R. Grace & Co., Danvers, MA) microconcentrators from Amicon. Five HPLC systems were used for analyses and sample separations: System I consisted of LKB 2150 pump, and 2152 controller, a UV detector - LKB 2238 UV Cord, a Berthold LB 506 A HPLC Radioactivity Monitor (of the International Berthold Group) and a Gilson Fraction collector 201-202 (Gilson International, Middleton, WI); System II was equipped with an auto-sampler, WISP 710 B, two pumps (model 510) and an automated gradient controller (of Waters Associates), a Perkin-Elmer LC-75 spectrophotometric detector, a Beckman model 170 Radioisotope Detector, and a fraction collector (Frac-100 of Pharmacia); System III consisted of two Waters M-6000A pumps with a Waters 660 solvent Programmer, a Waters Model 481 Variable Wavelength Detector, and a Waters Data Module, also an ISCO fraction collector was used preparatively; System IV was Dionex BioLC™ System equipped with a variable wavelength UV detector; and System V was a Waters Model 590 Pump with an ISCO Model 2360 gradient programmer and a Dionex variable wavelength detector. For centrifugation and concentration, a Sorvall RT 6000B (refrigerated centrifuge of Du Pont) was used. A Speed Vac concentrator (Savant Instruments Inc., Hicksville, N.Y.) was employed for removal of volatile solvents. Radioactivity measurements were done on a Capintec™ Radioisotope Calibrator (Trademark of Capintec Inc.) CRC-12, or by liquid scintillation on Beckman LS 9800 (Beckman Instruments, Inc., Irvine, CA), or on a Canberra 35⁺ multichannel analyzer interfaced with a 7.62 cm (3 in.) thallium drifted soldium iodide well crystal. In the examples concerning formation of complex, the percent complex determination was performed by the following general method where indicated. Percent Complex Determination by Cation Exchange A 10 ml plastic column was filled with 1 to 2 ml of SP-Sephadex™ C-25 resin which was swelled in water. The excess water was removed by applying pressure to the top of the column. The test solution (15 µl) was added to the top of the resin, then 2 ml of 4:1 (V:V) of isotonic saline: conc. NH₄OH was used as an eluent. The eluent was collected in a counting tube. An additional 2 ml of eluent was used. After collection of eluent into a second counting tube, air pressure was applied to the top of the resin to bring it to dryness. The dried resin was transferred to a third counting tube. The activity of each counting tube was measured with a NaI well counter coupled to a Canberra multichannel analyzer. The amount of the metal as a complex was given as the percentage of the total activity that was found in the eluent. The amount of metal in the free uncomplexed state was given as the percentage of the total metal that remains in the resin. Removal of Uncomplexed Metal by Ion Exchange A 10 ml plastic column was filled with 0.5 ml of SP-Sephadex™ C-25 resin swelled in water. The excess water was removed by centrifuging the column at 3,000 rpm for 4 min. A volume of 200-500 µl of the complex solution was placed at the top of the resin and the tube centrifuged again for 4 minutes at 3,000 rpm. The uncomplexed metal remained in the column and the complexed metal eluted with the solvent. Yttrium Complex Preparation: Complexes were made by preparing a 3 x 10⁻⁴M yttrium solution in water (YCl₃·6H₂O, 303.26 g/mole; or Y(OAc)₃, 12.1% H₂O). Radioactive Y³⁺ solution (Oakridge National Laboratories) was added to give the desired level of radioactivity. Ten µl of ligand solution (at 0.03M) was added to 990 µl of the Y³⁺ solution, giving a 1:1 molar ratio of ligand:metal. Ten times the amount of ligand solution was used for a 10:1 ligand to metal ratio. The pH was adjusted to 7.4 using microliter quantities of HCl or NaOH. The solution was then tested for the amount of complexed yttrium using the cation exchange method given above. Samarium Complex Preparation: Samarium complexes were formed as described above for yttrium complexes except that 3 x 10⁻⁴M samarium was prepared by dissolution of Sm₂O₃ (348.7 g/mole) in 0.1M HCl. Radioactive Sm-153 was obtained as an about 3 x 10⁻⁴M solution in 0.1M HCl from the University of Missouri Research Reactor, Columbia, Missouri. The following definitions are provided for some terms that are used throughout this text. Glossary: Conc. means concentrated; ⁻OAc means the acetate moiety, ⁻OCOCH₃; TLC means thin layer chromotography; DI H₂O means deionized NANOpure™ water; NANOpure™ water is pure water obtained from a Barnstead NANOpure™ water filtration system; Ambient temperature means room temperature or about 20 to about 25°C; Overnight means from about 9 to 18 hours; LC means liquid chromatography; NBS means N-bromosuccinimide; MES means 2-(N-morpholino)ethanesulfonic acid ; HPLC means high performance liquid chromatography; PBS means phosphate buffered saline from Sigma, containing 120 mM NaCl, 2.7 mM KCl and 10 mM phosphate buffer, pH 7.4; SP-Sephadex™ C-25 resin is a cation exchange resin having sulfonic acid functionality, sold by Pharmacia, Inc.; rpm = revolutions per minute; pD means pH where the hydrogen is deuterated; DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; HEPES = N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid; BFC = bifunctional chelant; Cyclen = 1,4,7,10-tetraazacylododecane; PA-DOTA = α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; PA-DOTMA = α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-acetic-4,7,10-tris(methylacetic) acid; BA-DOTA = α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; OMe-BA-DOTA = α-(5-amino-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; EA-DO3A = 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid; DTPA = diethylenetriaminepentaacetic acid; SCN-Bz-DTPA = 1-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid; EDTA = ethylenediaminetetraacetic acid; chelant is equivalent to ligand; complex is equivalent to chelate, e.g. a chelant, linked to a suitable metal ion; conjugate means a chelant or complex covalently attached to an antibody or antibody fragment; and antibodies means CC-49, CC-83 and B72.3 and their fragments such as Fab and F(ab′)₂. Other possible antibodies are given hereinbefore. The hybridoma cell line B72.3 is deposited in the American Type Culture Collection, having the accession number ATCC HB 8108, and the other named murine monoclonal antibodies bind to epitopes of TAG-72, a tumor associated antigen. The invention will be further clarified by a consideration of the following examples, which are intended to be purely exemplary of the use of the invention. Preparation of Starting Materials Example A Preparation of d,l -2-bromo-4-(4-nitrophenyl)butanoic acid, methyl ester. To a solution of 5 ml of carbon tetrachloride and 15 ml (0.2 mole) of thionyl chloride was added 10.46 g (0.05 mole) of 4-(4-nitrophenyl)butanoic acid under a nitrogen atmosphere. The solution was brought to reflux for 1 hour with initial liberation of hydrogen chloride gas and sulphur dioxide gas. To the warm solution was added 11-0 g (0.06 mole) of N-bromosuccinimide in 25 ml of carbon tetrachloride and three drops of 48 percent aqueous hydrogen bromide catalyst. Bromine gas liberation was noted. The dark red solution was refluxed for 35 minutes. The solution was cooled and poured into 100 ml of methanol with stirring. TLC analysis (60:40 ethylacetate:hexane v:v) indicated a new product (R f = 0.69, silica plates). The excess solvent was removed by rotary evaporation and the dark red oil was filtered through a flash silica gel pad (2.54 x 12.7 cm) (1 in. x 5 in.) using methylene chloride as the eluent. Evaporation of the solvent gave a clear oil, yield 15.43 g, which was a 85:15 mixture of the titled product: methyl ester of the starting butanoic acid derivative. The titled product was characterized by: ¹H NMR (CDCl₃) 8.16(d), 7.38(d), 4.20(dd), 3.79(s), 2.88 (m), 2.38(m); ¹³C NMR (CDCl₃, 75 MHz) 169.6, 147.5, 129.3, 123.7, 53.0, 44.4, 35.5, 33.0. Example B Preparation of α-[2-(4-nitrophenyl)ethyl]-1,4,7,10 -tetraazacyclododecane-1-acetic acid, 1-methyl ester. To a stirred solution of 1.72 g (10.0 mmole) of 1,4,7,10-tetraazacyclododecane in 17 ml of pentene stabilized chloroform was added 2.07 g (5.82 mmole) of d , l -2-bromo-4-(4-nitrophenyl)butanoic acid, methyl ester (prepared by the procedure of Example A) over five minutes under a nitrogen atmosphere with stirring. The reaction mixture was stirred for 48 hours at about 25°C. TLC (using Solvent System 2, on Analtech silica gel plates) indicated the formation of the title product (R f = 0.73). The yellow chloroform solution was applied to a 2.54 x 40.62 cm (1 inch x 16 inch) flash silica gel column (pre-eluted with 5 percent methanolic chloroform), eluted with 250 ml of 5 percent methanolic chloroform, followed by elution with Solvent System 2. Fractions containing pure title product were combined and evaporated to provide 2.15 g (5.46 mmole, 94 percent) of the title product as a light yellow glass. Trituration of a chloroform solution of this glass with diethyl ether resulted in precipitation of a white powder (MP = 156-59°C.) of analytical purity and characterized by: ¹H NMR (CDCl₃) 8.14(d), 7.39(d), 3.71(s), 3.39(dd), 2.5-3.0(m), 2.08(m), 2.01(m); ¹³C NMR (CDCl₃, 75 MHz) 172.7, 149.3, 146.4, 129.2, 123.6, 62.3, 51.2, 48.9,. 47.2, 45.8, 45,4, 32.8, 30.9. Example C Preparation of 2-bromo-2-(4-nitrophenyl)ethanoic acid, methyl ester. A mixture of p-nitrophenylacetic acid (25.0 g, 0.14 mole) and thionyl chloride (15.1 ml, 0.21 mole) in dry benzene (100 ml) was stirred at reflux under a N₂ pad for three hours. The mixture was then evaporated to dryness in vacuo. The residue was dissolved in carbon tetrachloride and stirred at reflux under a nitrogen pad. Bromine (7.2 ml, 0.14 mole) was added in small portions over a period of three days to the refluxing mixture. The reaction mixture was allowed to cool and the acid chloride was quenched with methanol (50 ml, added slowly). The resulting bromoester (27 g, 71 percent) was recovered as a yellow oil by distillation at reduced pressure (BP = 168°C. at 1.1 mm) through a six-inch column of glass helices. The structure of the title product was confirmed by: ¹H NMR (CDCl₃) 8.25(d), 7.81(d), 5.51(s), 3.86(s). Example D Preparation of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1-acetic acid, 1-methyl ester. To 529 mg (2.068 mmole) of 2-bromo-2-(4-nitrophenyl)ethanoic acid, methyl ester (prepared by the procedure of Example C) in 20 ml of acetonitrile was added all at once a solution of 354 mg (2.068 mmole) of 1,4,7,10-tetraazacyclododecane in 20 ml of acetonitrile containing just enough methanol to effect complete solution. The resulting pink solution was stirred for 1.5 hours then concentrated in vacuo at 35°C to a low volume. This crude monoestertetraamine was purified by silica gel chromatography eluting with 20 percent (wt/v) NH₄OAc/CH₃OH. The purified monoestertetraamine thus isolated as the triacetate salt was then converted to the free amine. Thus, 270 mg in 3 ml of water was treated at 0°C with aqueous K₂CO₃ (10 percent wt/wt) to a pH of 11. The basic solution was then extracted with 10 ml of chloroform, five times, and the chloroform layers combined, dried over sodium sulfate and concentrated to give 160 mg (42 percent yield) of the desired monoestertetraamine, characterized by NMR and fast atom bombardment mass spectrometry ([M+H]⁺=366) and by: ¹H NMR (CDCl₃) 8.12(d), 7.44(d), 4.75(s), 3.76(s), 2.67-2.44(m); ¹³C NMR (CDCl₃) 171.5, 147.6, 144.0, 130.0, 124.0, 67.0 49.8, 47.9, 46.9, 46.0. Example E Preparation of N-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane. To a stirred chloroform solution (20 ml) containing 2.9 g of 1,4,7,10-tetraazacyclododecane (16.8 mmole) was added a chloroform solution (20 ml) containing 2.1 g of 2-methoxy-5-nitrobenzyl bromide (8.5 mmole) in one portion. After stirring at room temperature for three hours the reaction mixture was filtered and the filtrate concentrated ( in vacuo ) to give a residue which was chromatographed (silica, Solvent System 3). The monoalkylated product was isolated in 79 percent yield (MP = 154-156°C), and characterized by: ¹³C NMR (CDCl₃) 162.47, 140.63, 127.92, 125.49, 124.53, 109.91, 55.88, 53.25, 50.90, 47.18, 45.45, 45.29. Example F Preparation of N-(2-hydroxy-5-nitrobenzyl)1,4,7,10-tetraazacyclododecane. To a 1,4-dioxane solution (20 ml) of 1,4,7,10-tetraazacyclododecane (2.3 g, 14 mmole) was added a dioxane solution (15 ml) of 2-hydroxy-5-nitrobenzyl bromide (1.2 g, 7 mmole) in one portion with constant stirring. After several minutes K₂CO₃ (1 g) was added and stirring continued for 1 hour at room temperature. The reaction mixture was then filtered and the filtrate concentrated in vacuo to give a yellow semi-solid which was chromatographed (column) on silica gel eluting with Solvent System 5. The desired mono-alkylated product was isolated from the last 1/3 of bright yellow eluent which also contained unreacted amine. After concentration, the yellow oil was triturated with CHCl₃ (100 ml) and filtered to remove CHCl₃-soluble amine starting material. The final product was then isolated in pure form as a yellow solid (1.2 g, 55 percent); (MP = 142-145°C) and further characterized by: ¹³C NMR (D₂O) 25.04, 25.28, 26.83, 31.80, 36.54, 101.88, 107.22, 110.92, 111.80, 115.26, 159.99. Example G Preparation of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane. To a stirred solution of 3.50 g (20.3 mmole) of 1,4,7,10-tetraazacyclododecane in 50 ml of pentene stabilized chloroform was added dropwise over a five minute period with vigorous stirring under a nitrogen atmosphere 4.00 g (17.4 mmole) of 1-(2-bromoethyl)-4-nitrobenzene. Stirring was continued for about 18 hours at room temperature (about 25°C) whereupon crystals of amine hydrobromide precipitated from solution. The entire reaction mixture was applied to a flash silica gel column (2.54 x 45.72 cm) (1 in x 18 in) which had been pre-eluted with 5 percent methanol in chloroform; 200 ml of this solution was applied as an eluent, followed by elution with Solvent System 3. From the desired product was separated 1.45 g (9.7 mmole) of p-nitrostyrene (R f = 0.98; Solvent System 1). The desired monofunctional title product was isolated as an orange-yellow oil (2.27 g, 7.06 mmole, 40.6 percent) which solidified upon standing (R f = 0.73, Solvent System 1). A sample of the titled product was recrystallized from CHCl₃/cyclohexane and showed the following characteristics: MP = 146.5-148.5°C; ¹H NMR (CDCl₃) 8.135(d, m), 7.395(d, m), 2.91(t), 2.77(t), 2.72(t), 2.50(t), 2.60(s); ¹³C NMR (CDCl₃, 75 MHz) 148.5, 146.7, 129.6, 123.4, 55.5, 51.4, 46.9, 45.9, 45.1, 33.7. Example H Preparation of 1-(4-nitrobenzyl)-1,4,7,10-tetraazacyclododecane. In 50 ml of chloroform was added 3.5g (20.3 mmole) of 1,4,7,10-tetraazacyclododecane and 1.7g (7.87 mmole) p-nitrobenzyl bromide and the mixture stirred under nitrogen for 24 hours at 25°C. The chloroform slurry of hydrobromide salt was then applied to a 1 in. x 17 in. column of flash silica gel (Solvent System 3). There was obtained 2.13 g (6.93 mmole) of the title product as a pale yellow solid of analytical purity in 88 percent yield (R f = 0.58, Solvent System 3), MP = 128-129°C, and further characterized by: ¹H NMR (CDCl₃) 8.19 (d), 7.49 (d), 3.69 (s), 2.82 (t), 2.70 (t), 2.59 (m); ¹³C NMR (CDCl₃, 75 MHz) 147.2, 128.4, 123.8, 58.8, 51.7, 47.1, 46.3, 45.1. (No Example I; to avoid confusion with later biology example numers). Example J Preparation of 1-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane. In 10 ml of methanol was dissolved 690 mg (2.25 mmole) of 1-(4-nitrobenzyl)-1,4,7,10-tetraazacyclododecane (prepared by the procedure of Example H). To the solution was added 350 mg of 10 percent palladium on carbon catalyst. Excess hydrogen was purged through the solution at 25°C. Within 45 minutes TLC indicated that the title product was prepared (R f = 0.33, Solvent System 3). Chromatographic purification of the formed titled product was conducted on 1 in. x 16 in. flash silica column (Solvent System 3) and provided 480 mg (77 percent) of the title product as a pale yellow, clear oil. The free base title product (103 mg, 0.37 mmole) was converted to the hydrochloride salt by bubbling anhydrous hydrogen chloride through ethanol solutions of the free base. The resulting tetrahydrochloride salt of the title product, after washing with cold ethanol and drying in vacuo, was obtained in a yield of 147 mg (0.347 mmole), MP = 255-260°C (dec), and was further characterized by: ¹H (D₂O, pD = 1.9) 7.56 (d), 7.47 (d), 3.95 (s), 3.28 (t), 3.23 (t), 3.09 (t), 2.96 (t); ¹³C NMR (D₂O, pD = 1.9, 75 MHz) 138.3, 134.2, 132.2, 126.0, 58.5, 50.3, 46.7, 44.6, 44.3. Example K Preparation of 2-methoxy-5-nitrobenzylnitrile. To a solution of sodium cyanide (6 g, 121.9 mmole) in water (5.3 ml) at 70°C was added in small portions with stirring a hot solution of 2-methoxy-5-nitrobenzylbromide (25 g., 101.6 mmole) in ethanol (15 ml). The reaction mixture was then refluxed for 1.5 hours, cooled, and filtered. The filter cake was washed with acetonitrile and the filtrate was evaporated in vacuo to yield 2-methoxy-5-nitrobenzylnitrile (19.5 g., 100 percent) as a tan solid. The product was characterized by: ¹³C NMR (CDCl₃) 161.4, 141.0, 125.7, 124.6, 119.8, 116.5, 110.2, 56.3, 18.8. Example L Preparation of 2-methoxy-5-nitrophenylacetic acid. A slurry of 2-methoxy-5-nitrobenzylnitrile (19.5 g) (prepared by the procedure of Example K) in conc. HCl (20 ml) was refluxed for three hours. After cooling, the crude product was recovered by filtration and washed with water. The solid was taken up in hot aqueous sodium hydroxide and filtered while hot. The orange solution was cooled and acidified with HCl. The precipitate was filtered, washed with water, and dried to yield 2-methoxy-5-nitrophenylacetic acid as a white solid (15 g, 70 percent). The product was characterized by: ¹³C NMR (CDCl₃-CD₃OD) 172.8, 162.5, 140.7, 126.2, 124.7, 124.1, 109.7, 55.8, 35.0. Example M Preparation of α-bromo-(2-methoxy-5-nitrophenyl)acetic acid, methyl ester. To a slurry of 2-methoxy-5-nitrophenylacetic acid (2.266 g, 10.74 mmole) (prepared by the procedure of Example L) in dry benzene (50 ml) was added thionyl chloride (4.0 ml, 54.8 mmole). A drying tube and condenser were placed on the flask and the mixture was refluxed for 2 hours. The resulting yellow solution was concentrated in vacuo to a small volume and taken up in dry carbon tetrachloride. Bromine (0.6 ml, 11.6 mmole) was added and the solution was refluxed for two days with the exclusion of atmospheric moisture. The reaction mixture was concentrated to a small volume and methanol (50 ml) was added. After evaporation of excess methanol in vacuo the resulting oil was purified chromatographically (silica gel, methylene chloride-hexane 4:1). The title product (2.399 g., 74 percent) was obtained as a yellow oil. The product was characterized by: ¹H NMR (CDCl₃) 8.45(dd), 8.15(dd), 6.95 (d), 5.75(s), 3.99(s), 3.78(s). Example N Preparation of α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane, 1-acetic acid, methyl ester. A solution of α-bromo (2-methoxy-5-nitrophenyl)-acetic (2.399 g, 7.89 mmole) (prepared by the procedure of Example M) in chloroform (10 ml) was added to a stirred solution of 1,4,7,10-tetraazacyclododecane (2.72 g, 15.79 mmole) in chloroform (50 ml). The mixture was stirred at room temperature for 2 hours. The cloudy mixture was then concentrated to a small volumn in vacuo at room temperature. The crude product was purified by chromatography (silica gel, Solvent System 3). The title compound was recovered as a yellow solid (2.60 g, 83 percent) and characterized by: ¹³C NMR (CDCl₃) 170.7, 161.6, 139.9, 125.0, 124.5, 124.2, 110.2, 59.5, 55.5, 50.5, 48.0, 47.3, 45.6, 44.3, 43.5. Example O Preparation of d,l -2-bromo-4-(4-nitrophenyl)butanoic acid isopropyl ester. 4-(4-Nitrophenyl)butanoic acid (21.0 g, 0.10 mole) was added to a solution of carbon tetrachloride (10 ml) and thionyl chloride (30 ml, 0.4 mole) under a nitrogen atmosphere using the procedure of Harpp et al., J.Org.Chem 40 , 3420-27 (1975). The solution was brought to reflux for 1 hour with initial rapid liberation of hydrogen chloride and sulfur dioxide. At this point; N-bromosuccinimide (22.0 g, 0.12 mole) was added as a solution in carbon tetrachloride (50 ml) and 8 drops of 48% aqueous hydrogen bromide catalyst was added to the warm solution whereupon bromine liberation was noted. The dark red solution was refluxed for an additional 35 minutes. The solution was cooled and poured into isopropanol (400 ml) with stirring. TLC analysis (methylene chloride, silica gel plates) revealed a new product (R f =0.73). The excess solvent was removed and the dark red oil was filtered through a flash silica gel pad (7.62 x 15.24 cm) (3 in. x 6 in.) using methylene chloride as an eluent. The solvent was removed in vacuo and the light yellow oil was applied to a flash silica gel column (3 in. x 18 in.) and eluted with methylene chloride to afford 25.0 g (0.076 mole) of the titled bromoester product as a clear oil in 75% yield as a isopropanol solvate which contained less than 5% of unbrominated ester and characterized by: ¹H NMR (CDCl₃) 8.16(d, 2H), 7.38(d, 2H), 5.05(septet, 1H), 4.14(dd, 1H), 2.88(m, 4H), 2.39(m, 4H), 1.29(d, 6H); ¹³C NMR (CDCl₃) 168.7, 147.7, 129.3, 123.8, 69.9, 45.1, 35.6, 33.0, 21.5, 21.2. Example P Preparation of α-[3-(4-nitrophenyl)propyl]-1,4,7,10-tetraazacyclododecane-1-acetic acid, 1-methyl ester. To a stirred solution of 3.137 g (18.2 mmoles) of cyclen free base in 30 ml of pentene stabilized chloroform was added 4.81 g (14.6 mmoles corrected) of d,l -2-bromo-4-(4-nitrophenyl)-butanoic acid isopropyl ester (prepared by the procedure of Example O) over a 5 minute period under a nitrogen atmosphere with stirring. The reaction solution was stirred for 24 hours at room temperature. TLC analysis (Solvent System 2) revealed conversion to the titled monoalkylation product (R f =0.78 detection withninhydrin, iodine, and UV activity). The yellow chloroform solution was applied to a 2.54 x 43.18 cm (1 in. x 17 in.) flash silica gel column which had been pre-eluted with 5% methanolic chloroform. Elution with 300 ml of this solvent system was followed by elution with Solvent System 2 and provided fractions containing pure titled product which were combined and evaporated affording 4.85 g (5.46 mmoles) of the titled product free base as a light oil in 79% yield and further characterized by: ¹H NMR (CDCl₃) 8.15(d, 2H), 7.40(d, 2H), 5.07(p, 1H), 3.35(dd, 1H), 2.65-3.0(m, 13H), 2.5-2.64(m, 4H), 2.14(m, 1H), 2.00(m, 1H), 1.28(dd, 6H); ¹³C NMR (CDCl₃) 171.6, 149.5, 146.5, 129.2, 123.6, 68.1, 62.7, 49.2, 47.5, 45.9, 45.7, 32.9, 31.0, 22.1, 22.0; IR (CDCl₃) cm⁻¹ 3231(N-H), 2978, 2933, 1721 (ester carbonyl), 1601, 1512, 1458, 1345, 1107; Fast atom bombardment mass spectrum, m/e 422 (M+H)]+, 408, 392. Preparation of Final Products - Ligands Example 1 Preparation of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, monomethyl, triethyl ester. In 46 ml of acetonitrile containing 4.6 g (33.3 mmole) of freshly powdered anhydrous potassium carbonate was dissolved 700 mg (1.91 mmole) of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1-acetic acid, 1-methyl ester (prepared by the procedure of Example D). To this suspension was added all at once 1.022 g (6.12 mmole) of ethyl bromoacetate. After four hours of stirring at room temperature, the suspension was vacuum filtered, the filter cake washed with 15 ml of acetonitrile, two times, and the filtrate evaporated in vacuo at 38°C to give the crude titled tetraester as a purple solid. The tetraester was then purified by silica gel chromatography eluting with 5 percent C₂H₅OH/CHCl₃ then Solvent System 3, to give 620 mg (0.988 mmole, 52 percent) of the desired product. This product was characterized by fast atom bombardment mass spectrometry ([M+H]⁺=624) and futher characterized by: ¹H NMR (CDCl₃) 8.24(d), 7.45(d), 4.94(s), 4.35-4.10(m), 3.79(s), 3.75-1.84(m), 1.34-1.22(m); ¹³C NMR (CDCl₃) 174.3, 173.8, 173.6, 171.5, 147.6, 138.9, 131.5, 123.4, 64.8, 61.5, 61.4, 60.2, 55.4, 55.0, 53.1, 52.9, 52.7, 52.4, 51.9, 51.7, 48.8, 48.3, 44.9, 19.1, 14.1. Example 2 Preparation of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. In 30 ml of 6N HCl was dissolved 300 mg (0.478 mmole) of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, monomethyl, triethyl ester (prepared by the procedure of Example 1) and the mixture was heated at reflux overnight. At the end of this reflux period, the solution was concentrated in vacuo at 70°C to give a yellow solid. This solid was dissolved in 3 ml of water, filtered, and the filtrate evaporated to give 253 mg (0.378 mmole, 79 percent) of the crude product. This product was purified by preparative TLC [silica gel, developed in 20 percent NH₄OAc/CH₃OH (wt/v)] and characterized by fast atom bombardment mass spectrometry ([M+H[⁺=526) and futher characterized by: ¹H NMR (D₂O) 8.21(d), 7.42(d), 4.83(s), 3.83-2.19(m), 1.92(s); ¹³C NMR (D₂O) 175.0, 173.6, 171.8, 167.0, 166.3, 146.9, 138.3, 130.1, 123.0, 62.2, 54.0, 53.0, 52.2, 50.4, 97.3, 46.8, 44.8, 42.8, 20.0. Example 3 Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; (BA-DOTA). Method A: Catalytic hydrogenation of the nitro group of the tetraacid (prepared by the procedure of Example 2) was performed using Adams catalyst (PtO₂) and hydrogen in essentially quantitative yield to give the titled product. This product was characterized by fast atom bombardment ([M+H]⁺=496) and anion exchange HPLC (on Q-Sepharose™) and futher characterized by: ¹H NMR (D₂O) 8.12(d), 7.86(d), 5.66(s), 4.73-4.57(m), 4.27-3.78 (m), 3.39-2.91(m); ¹³C NMR (D₂O) 176.54, 176.52, 176.46, 141.1, 128.9, 120.9, 112.5, 65.0, 55.9, 55.7, 53.6, 49.7, 49.5, 49.3, 45.7, 45.4, 44.9, 44.6, 41.4. Method B: Another method to synthesize this compound was to convert the monoester tetraamine compound from Example D to the monoacid tetraamine compound (6N HCl, reflux overnight), followed by aqueous alkylation using bromoacetic acid, then reduction of the nitro group to the amine group (PtO₂ catalyst) to give a product identical to that described above. Example 4 Preparation of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid. In 60 ml of 6N HCl was dissolved 2.0g (5.48 mmole) of the monoester tetraamine compound (prepared by the procedure of Example D). The mixture was heated to 95°C overnight (about 10 hours) after which it was concentrated in vacuo at 75°C to give 2.53 g (5.11 mmole, 96 percent) of the monoacid tetraamine tetrahydrochloride as a yellow solid. The above monoacid tetraamine tetrahydrochloride (0.5 g, 1.0 mmole) was dissolved in 15 ml of water and adjusted to pH 9 with NaOH. A separate solution of bromoacetic acid was prepared (0.71 g, 5.13 mmole) and added to the water solution of the monoacid tetraamine. The pH of the solution was again adjusted to 9 and maintained at this pH during the reaction by small additions of 1.0N NaOH. While the reaction was stirred, aliquots were removed at different time points and the progress of the alkylation was monitored by anion exchange HPLC. When the amount of dialkylation product (total of three acetate groups present) had reached a maximum, the whole reaction mixture was lyophilized to give a dark solid. This crude mixture of alkylated products was then purified by silica gel chromatography (eluting with Solvent System 1), followed by preparative anion exchange chromatography (eluting with a gradient of 0-100 percent 1M NH₄OAc), then by preparative TLC plates (developed in Solvent System 4) and finally by silica gal chromatography (eluting with Solvent System 4). This extensive purification procedure gave, as a yellow solid, 30 mg (0.06 mmole, 6.0 percent) of the title product. This product was characterized by fast atom bombardment mass spectrometry ([M+H]⁺=468), anion exchange HPLC and futher characterized by: ¹H NMR (D₂O) 8.12(bs), 7.35(bs), 4.76(s), 3.57-3.44(m), 2.97-1.83(m), 1.80(s); ¹³C NMR (D₂O) 181.75, 180.68, 179.00, 175.37, 147.70, 141.22, 133.08, 123.53, 68.44, 59.72, 56.00, 52.80, 49.96, 49.29, 47.86, 45.36, 44.26, 42.78, 42.25, 23.72. Example 5 Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid pentahydrochloride and α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,10-triacetic acid pentahydrochloride. A crude mixture of alkylated products was prepared by the procedure described in Example 4. This crude mixture was chromatographed on a silica gel column eluting with 20 percent NH₄OAc/CH₃OH (wt:v). The appropriate fractions from this column were combined and evaporated to dryness. The crude product, having substantial amounts of NH₄OAc, was dissolved in 80 ml of NANOpure™ water and lyophilized to yield a light brown solid. This solid was dissolved in 20 ml of NANOpure™ water, shaken with PtO₂ catalyst under a H₂ atmosphere until hydrogen uptake stopped. The catalyst was separated by vacuum filtration, add the filtrate lyophilized to give a yellow solid. The solid was dissolved in 3 ml of Solvent System 4 and chromatographed on silica gel using Solvent System 4. The pooled fractions were then stripped in vacuo and lyophilized to yield 779.6 mg of light yellow solid. ¹³C NMR and proton NMR suggests that this product is a 50/50 mixture of the two possible geometric isomers. The isomeric mixture was contacted with excess HCl and lyophilized to yield 548.4 mg (61 percent yield) of the title products. M.P.>270°C. Anion exchange chromatography (HPLC System III) showed one major peak (>94 percent purity); fast atom bombardment mass spectrum indicated the geometrical isomers [M+H]⁺ = 438. Example 6 Preparation of α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester. To a solution of 1.43 g (3.63 mole) of α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-acetic acid, 1-methyl ester (prepared by the procedure of Example B) in 40 ml of argon purged acetonitrile was added 1.71 g (12.34 mmole) of anhydrous potassium carbonate with vigorous stirring. To the reaction mixture was added 1.78 g (11.61 mmole) of methyl bromoacetate and the reaction mixture was stirred at about 25°C for 48 hours. TLC analysis indicated formation of a new product (R f = 0.62, Solvent System 2). To the slurry was added 6.0 g of flash silica gel and acetonitrile was removed on a rotary evaporator. The resulting material was applied to 2.54 x 40.64 cm (1 in. x 16 in.) silica column which had been pre-eluted with 5 percent methanolic chloroform. About 400 ml of the prepared solution was used to elute several nonpolar impurities and unreacted alkylating agent. Then Solvent System 2 was applied, fractions containing product (R f = 0.62) were collected, combined and evaporated to provide 2.1 g (3.44 mmole, 95 percent) of the titled product as a pale yellow glass. ¹H NMR indicated this product to be a 2:1 mixture of conformational or geometric isomers. ¹H NMR (CDCl₃, 50°C) 8.137(d), 8.128(d), 7.398(d), 7.385(d), 3.82(s), 3.76(s), 3.75(s), 3.74(s), 3.68(s), 1.5-3.52(m); ¹³C NMR (CDCl₃, 50°C, 75 MHz) 175.8, 174.2, 174.1, 174.0, 149.0, 129.5, 129.3, 123.6, 60.1, 55.1, 52.8, 52.7, 52.6, 52.4, 52.2, 52.1, 52.0, 51.2, 51.1, 51.0, 49.1, 48.8, 47.5, 45.2, 34.2, 32.6. Example 7 Preparation of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester. In 25 ml of methanol containing 400 mg of 10 percent palladium-on-carbon catalyst under a nitrogen atmosphere was dissolved 1.41 g (2.31 mole) of α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester (prepared by the procedure of Example 6). Excess hydrogen was purged through the solution at one atmosphere for three hours. TLC indicated the formation of a strongly ninhydrin positive material (R f =0.62, Solvent System 2). The methanolic catalyst slurry was filtered through celite and evaporation of solvent provided the title product, 1.21 g (2.08 mmole, 91 percent), as a white solid glass (as a 2:1 mixture of conformational isomers). The minor conformational or geometric isomer was separated from the major isomer by flash chromatrography using 10 percent methanolic chloroform to yield the title product as an off white powder (MP = 89-95°C) and characterized by: ¹H NMR (CDCl₃, 50°C) 6.94(d), 6.89(d), 6.69(d), 6.66(d), 3.91(s), 3.80(s), 3.78(s), 3.74(s), 3.73(s), 3.72(s), 3.71(s), 1.5-3.5(m); ¹³C NMR (CDCl₃, 50°C, 75 MHz) 176.1, 174.0, 173.9, 172.2, 170.4, 169.6, 144.2, 144.1, 130.6, 130.5, 129.5, 129.1, 115.9, 115.8, 62.6, 58.7, 55.1, 54.3, 52.7, 52.5, 52.3, 52.2, 52.1, 52.0, 51.9, 51.8, 51.7, 50.2, 50.0, 47.3, 44.7, 32.8, 31.8, 30.0, 25.2; Fast atom bombardment mass spectrum, m/e 602 [M+Na⁺], 618 [M+K⁺]⁺, [624 M+2Na⁺-H⁺]⁺. Example 8 Preparation of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; (PA-DOTA). In 50 ml of conc. hydrodrochloric acid was dissolved 1.5 g (2.59 mmole) of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester (as the crude 2:1 mixture prepared by the procedure of Example 7). The reaction mixture was refluxed at about 105°C for six hours. TLC (Solvent System 1) indicated conversion of the ester (R f = 0.88) to the title product as the hydrochloride salt (R f = 0.43). Excess solvent was removed on a rotary evaporator and the resulting white solid was dried. The title product as the hydrochloride salt was obtained in a yield of 1.6 g and characterized by: ¹H NMR (D₂O, pD = 1.0., 90°C) 7.48(d), 7.42(d), 2.8-4.3(m), 2.23(m), 2.03(m); ¹³C NMR (D₂O, pD = 1.0, 90°C, 75 MHz) 176.4, 174.9, 171.6, 144.7, 132.9, 132.8, 130.4, 125.7, 61.7, 56.8, 56.0, 53.7, 53.1, 51.6, 47.9,. 34.3, 37.6, Fast atom bombardment mass spectrum m/e 524 [M+H]⁺, 546 [M+Na⁺]⁺, 568 [M+2Na⁺-H⁺]⁺. Using flash chromatography and Solvent System 1, any trace impurities of the ester were removed from the title product as the hydrochloride salt. To a 2.54 x 58.42 cm (1 in. x 23 in.) flash silica gel column was applied 1.10 g of the title product, as the hydrochloride salt. Fractions containing only the title product, as the mixed ammonium potassium salt were combined to provide 580 mg. HPLC analysis indicated the material to be greater than 98 percent area purity at 230 and 254 nm. Fast atom bombardment mass spectrum, m/e 562 (M+K)⁺, 584 [M+K⁺+Na⁺-H⁺], 600 [M+2K⁺-H⁺]⁺. Example 9 Isolation of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,10-triacetic acid, mixed ammonium, potassium salt. A crude solution containing both the tetra and tri acids (2.05 g) (prepared by the procedure of Example 8) was dissolved in a minimum amount of Solvent System 1 and applied to a 30.48 x 7.62 cm (12 in. x 3 in.) column of flash silica gel which had been pre-eluted with this solvent. Elution of fractions containing the title product (R f = 0.63 in Solvent System 1) were collected and afforded 200 mg of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,10-triacetic acid, mixed ammonium, potassium salt. ¹H and ¹³C NMR analysis suggested that this triacid was the symmetrical isomer (1,4,10-triacid positional isomer): ¹H NMR (D₂O, pD = 0.5 with DCl, T = 90°C) 7.52(d), 7.46(d), 3.60(m), 3.54(m), 3.19(m); ¹³C NMR (D₂O, pD = 0.5, T = 90°C) 176.1, 170.2, 140.0, 132.7, 131.1, 126.1, 57.6, 57.2, 56.1, 54.9, 53.2, 51.5, 51.2, 31.2. Fast atom bombardment mass spectrum, m/e 466[M+H⁺]⁺, 488[M+Na⁺]⁺, 504[M+K⁺]⁺, 526[M+K⁺+Na⁺-H⁺⁺], 542[M+2K-H)]⁺. Example 10 Preparation of α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, tetramethyl ester. Methyl bromoacetate (565 µl, 5.97 mmole) was added to a stirred mixture of α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane, 1-acetic acid, methyl ester (580 mg, 1.47 mmole) (prepared by the procedure of Example N) and pulverized potassium carbonate (1.15 g, 8.32 mmole) in acetonitrile (20 ml). The reaction mixture was stirred at room temperature for 2 hours. The mixture was then filtered and the filtrate was concentrated to an oil in vacuo . The crude product was purified by chromatography (silica gel, 8 percent methanol in methylene chloride). The title product was obtained as a yellow solid (469 mg, 52 percent), TLC R f = 0.4 (silica gel, 10% CH₃OH in CHCl₃), and further characterized by: ¹³C NMR (CDCl₃) 173.2, 172.6, 161.2, 139.1, 125.1, 124.6, 120.5, 110.7, 57.0, 55.6, 53.5, 52.6, 51.3, 50.8, 46.8, 46.0, 44.0. Example 11 Preparation of α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. A solution of α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, tetramethyl ester (prepared by the procedure of Example 10) in concentrated HCl (5 ml, J.T. Baker ULTREX) was refluxed under a nitrogen atmosphere for 5 hours. The solution was then concentrated to dryness in vacuo to leave a solid residue. This was purified by chromatography (silica gel, Solvent System 6) to yield the title product as an off-white solid (209 mg). This material was converted to the tetrahydrochloride salt and was characterized by: ¹³C NMR (D₂O-DCl, 80°C) 171.0, 166.9, 161.2, 139.0, 125.5, 119.3, 110.7, 56.8, 54.5, 52.7, 51.0, 49.2, 49.0, 46.3, 42.9. Example 12 Preparation of α-(2-methoxy-5-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, tetraammonium salt. To a solution of α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (157 mg) (prepared by the procedure of Example 11) in water (20 ml) was added platinum oxide (20 mg). This mixture was hydrogenated (1 atmosphere hydrogen) for 1 hour at room temperature. After filtration, the material was further purified by chromatography (silica gel, Solvent System 5) to yield the title compound (141 mg) as an off-white solid, and characterized by: ¹³C NMR (D₂O)-DCl) 175.5, 172.6, 172.3, 159.9, 128.8, 127.5, 124.6, 123.8, 115.5, 61.2, 58.1, 57.3, 55.7, 53.4, 51.6, 49.6, 47.4. Example 13 Preparation of 1-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-triacetic acid, 4,7,10-trimethyl ester. To 4 ml of argon purged acetonitrile with stirring was added 100 mg (0.236 mmole) of 1-(4-aminobenzyl)-1,4,7-10-tetraaacyclododecane, tetrahydrochloride salt (prepared by the procedure of Example J), 260 mg (1.88 mmole) of potassium carbonate, and 108 mg (0.708 mmole) of methylbromoacetate. The mixture was stirred for 48 hours at 25°C. The salt containing solution was applied to a 1 cm x 4 cm flash silica gel column and was eluted with acetonitrile. Fractions containing the desired product were combined and the solvent removed by rotary evaporation to provide 65 mg (0.132 mmole, 56 percent) of the title product which was further characterized by: ¹H NMR (CDCl₃) 7.29 (d), 6.75 (d), 4.62 (s), 4.20 (broad s), 3.70 (s), 3.69 (s), 3.64 (s), 3.62 (t), 3.27 (s), 3.06 (t), 2.82 (broad t), 2.79 (broad t); ¹³C NMR (CDCl₃, 75 MHz) 171.4, 171.0, 148.4, 132.8, 117.5, 115.0, 55.9, 55.3, 54.7, 53.1, 51.7, 51.4, 50.6, 50.5, 47.4. Example 14 Preparation of 1-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, hydrochloride salt. In 2 ml of 6N hydrochloric acid, 42 mg (0.085 mmole) of 1-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester (prepared by the procedure of Example 13) was heated to 80°C for 2 hours. TLC indicated several products (R f = 0.60 for the desired title product, Solvent System 1). Removal of solvent afforded 41 mg of crude title product. Example 15 Preparation of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10,-triacetic acid, 4,7,10-trimethyl ester. To a solution of 2.24 g (6.97 mmole) of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane (prepared by the procedure of Example G) in 75 ml of argon purged acetonitrile was added with vigorous stirring 3.17 g of anhydrous potassium carbonate. To this reaction mixture was added dropwise over a five minute period 3.20 g (20.9 mmole) of methylbromoacetate. The reaction mixture was stirred for 17 hours under argon atmosphere. TLC analysis showed conversion of the starting material (R f = 0.73, Solvent System 1) to a new product (R f = 0.46, Solvent System 1). To the solution was added 70 ml of chloroform and the solution with the suspended salt was applied to a 2.54 x 17.78 cm (1 in. x 7 in.) flash silica column. The product was eluted using 10 percent methanol in chloroform to yield 2.95 g of the title product as an amber oil which formed a friable glass upon vacuum drying (78 percent). The title product was characterized by: ¹H NMR (CDCl₃) 8.17 (m,m), 7.4-7.66 (m), 2.38-3.95 (m). ¹³C NMR (CDCl₃, 75 MHz) 171.5, 171.2, 146.7, 144.5, 130.3, 123.9, 56.0, 55.2, 53.5, 53.4, 52.6, 51.9, 51.8, 50.6, 48.1, 29.5. Example 16 Preparation of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester. In 50 ml of methanol was dissolved 2.8 g (5.18 mmole) of crude 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester (prepared by the procedure of Example 15). To the stirred solution which was purged with nitrogen was added 10 percent palladium on carbon catalyst (600 mg). The solution was maintained under an atmosphere of nitrogen, and then hydrogen (1 atm, 20-25°C) was purged through the stirred solution for 2.5 hours. The solution was then purged for several minutes with nitrogen and the catalyst removed by filtration through a short bed of celite. TLC analysis (10 percent methanol in chloroform) revealed the title product (R f = 0.14). The title product was eluted with chloroform from silica gel to yield 2.2 g (4.33 mmole, 83 percent) as a white glass and characterized by: ¹H NMR (CDCl₃) 7.03 (d,m), 6.63 (d), 3.4-3.6 (m), 2.7-3.2 (m); ¹³C NMR (CDCl₃, 75 MHz) 171.4, 171.2, 145.6, 129.7, 125.6, 115.5, 55.9, 54.4, 54.3, 53.0, 52.8, 51.8, 51.6, 50.3, 47.8, 28.6; Fast atom bombardment mass spectrum, m/e 508 [M+H⁺]⁺. Example 17 Preparation of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, hydrochloride salt; (EA-D03A). In 30 ml of conc. HCl was dissolved 850 mg (1.69 mmole) of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester (prepared by the procedure of Example 16). The solution was stirred at 70-80°C for 2.5 hours and the solution allowed to cool with stirring to 25°C and the stirring continued for about 18 hours. Solvent was removed on a rotary evaporator at reduced pressure (10 mm, 75°C). Solvate and excess hydrogen chloride were removed from the resulting clear oil by vacuum drying (10⁻¹ mm, 45°C). The title product was provided as a white solid, in a yield of 890 mg, (R f = 0.46, Solvent System 2) and further characterized by: ¹H NMR (D₂O, pD = 1.9, T = 90°C) 7.50(d), 7.41(d), 4.26(s), 3.43-3.68(m), 3.0-3.3(m); ¹³C NMR (D₂O, pD = 1.9, T = 90°C) 176.7, 170.9 139.8, 133.0, 131.2, 125.9, 57.5, 57.1, 55.4, 54.4, 52.7, 51.0, 50.6, 31.3; Fast atom bombardment mass spectrum, m/e 466 (M+H⁺), 488 [M+Na⁺], 510 [M+2Na⁺-H⁺]⁺. HPLC analysis indicated greater than 92 percent area purity (254 mm) using a 10 cm Partisil®-5 OD53 RAC II reverse phase column. The eluent was 10 percent acetonitrile in 0.05M pH = 7.0 potassium phosphate solution. Example 18 Preparation of 1-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid; (SCN-EA-DO3A). 1-[2-(4-Aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, hydrochloride salt (prepared by the procedure of Example 17, 106 mg, 0.21 mmole) was dissolved in 2 ml of water under a nitrogen atmosphere with stirring. Sodium bicarbonate (105.6 mg, 1.26 mmole) was slowly added to prevent frothing from carbon dioxide evolution (resulting pH = 8.0). Thiophosgene (16.8 µl, 0.22 mmole) was added and after one hour of vigorous stirring, TLC analysis (20 percent water in acetonitrile) indicated conversion of starting material (R f = 0.12) to title product (R f = 0.26). The solvent was removed from the crude product by rotary evaporation to afford 130 mg of title product which contained sodium chloride. Infrared analysis of this material (KBr pellet) confirmed the presence of the isothiocyanate moiety (SCN = 2150 cm⁻¹). Example 19 Preparation of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, triethyl ester. To 5 ml of a stirred acetonitrile solution containing 395 mg (1.12 mmole) of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane (prepared by the procedure of Example G) and 1.5 g (11 mmole) of K₂CO₃ was added 496 µl (4.5 mmole) of ethyl bromoacetate in one portion. After heating at 68°C under a N₂ atmosphere for one hour, the resulting suspension was filtered. The filter cake was washed with CH₃CN (2 x 10 ml). The filtrate was then concentrated to give the crude product as a viscous oil, triturated with 30 ml of diethyl ether, and concentrated to give 650 mg (100% yield) of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, triethyl ester and characterized by: ¹H NMR (CDCl₃) 8.2(d), 7.6(d), 4.3(q), 2.6-3.8(m), 1.55(t); Fast atom bombardment mass spectrum [M+H]⁺ = 588. Example 20 Preparation of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid. To a suspension of 200 mg (0.35 mmole) of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, triethyl ester (prepared by the procedure of Example 19) in 15 ml of water was added 59 µl of NaOH (50% wt/wt, 3 eq). The mixture was stirred at 80°C for 6 hours. The resulting homogeneous orange solution was then cooled to room temperature and freeze-dried to yield a brown solid which was purified by HPLC (Q-Sepharose™, HPLC System III) using a linear gradient of 0-10% aqueous HOAc over 60 minutes to yield (50%) of the hydrolyzed product 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triactic acid, and characterized by: ¹H NMR (D₂O) 8.22(d), 7.55(d), 3.60-3.90(m), 3.10-3.40(m). Example 21 Preparation of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid; (EA-DO3A). In a Parr-hydrogenater was placed 50 ml of an aqueous solution of 214 mg (0.43 mmole) of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid (prepared by the procedure of Example 20) and 40 mg of 10% Pd/C. The suspension was shaken until hydrogen uptake ceased. After filtration, the aqueous solution was freeze-dried yielding 197 mg (98%), as a tan solid, 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, and characterized by: ¹H NMR (D₂O) 7.35(d), 7.20(d), 3.10-3.70(m); ¹³C NMR (D₂O) 173.85, 172.50, 137.90, 131.90, 130.22, 121.55, 56.25, 55.14, 54.42, 50.12, 49.65, 49.31, 31.00. Example 22 Preparation of 1-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester. To a stirred acetonitrile solution (20 ml) containing 1.0g of 1-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane (3 mmole) (prepared by the procedure of Example E) was added 1.6g of methyl bromoacetate (11 mmole) in one portion. After one hour potassium carbonate (0.3 g) was added and stirring continued at room temperature for twelve hours. The reaction mixture was then filtered and the filtrate concentrated (in vacuo) . The resulting residue was column chromatographed (silica, CH₃CN/CH₃OH, 9:1, V:V) yielding the triester as a white solid in 68 percent yield after concentration, and was further characterized by: ¹H NMR (CDCl₃) 8.19(d), 8.14(s), 7.18(d), 2.58-3.99(m); ¹³C NMR (CDCl₃) 173.53, 172.83, 164.59, 142.28, 128.51, 127.69, 126.49, 112.30, 57.25, 56.90, 55.03, 54.21, 53.06, 52.09, 52.00, 51.54, 50.68, 50.30, 49.85, 49.63, 49.31, 49.00, 48.68,48.37, 48.05, 47.70, 47.39. Example 23 Preparation of 1-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid. A 6M hydrochloric acid solution (3 ml) containing 0.25 g of 1-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester (0.45 mmole) (prepared by the procedure of Example 22) was stirred and heated at 100°C for 24 hours. After cooling to room temperature, 5 ml of water was added and the aqueous solution freeze-dried to give a tan solid. Following column chromatography (silica, Solvent System 5) the triacid was isolated in 60 percent yield as an off-white solid, MP = 228-230°C (dec), and further characterized by: ¹H NMR (D₂O) 8.18(d), 8.09(s), 7.12(d), 3.87(s), 2.10-3.60(m); ¹³C NMR (D₂O) 180.45, 179.80, 163.66, 140.22, 128.60, 126.24, 122.66, 111.50, 59.91, 59.06, 56.44, 52.75, 50.92, 48.84. Example 24 Preparation of 1-(2-methoxy-5-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid. To a nitrogen purged aqueous (50 ml) solution containing 50 mg of PtO₂ was added 50 mg of 1-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid (prepared by the procedure of Example 23). After hydrogenating in a Parr bomb for one hour, the solution was filtered and the aqueous filtrate freeze-dried to give the aniline derivative as a tan solid (95 percent yield), MP>240°C dec, and further characterized by: ¹H NMR (D₂O) 7.54(bs), 7.21(d), 7.09(d), 7.05(s), 6.88(s), 3.84(s), 3.78(s), 2.85-3.56(m); ¹³C NMR (D₂O) 180.59, 179.77, 153.38, 124.16, 124.03, 122.82, 120.18, 113.68, 112.43, 59.06, 57.02, 55.96, 53.67, 50.52, 50.08,49.70, 49.04, 48.32. Example 25 Preparation of 1-(2-hydroxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecene-4,7,10-triacetic acid. To an aqueous solution (1 ml) of 1-(2-hydroxy-5-nitrobenzyl-1,4,7,10-tetraazacyclododecane (200 mg, 0.62 mmole) (prepared by the procedure of Example F) was added bromoacetic acid (309 mg, 2.2 mmole, and NaOH (3.5 ml, ≈ 1M) with stirring at room temperature. The reaction progress was monitored by LC (anion exchange, Q-Sepharose™) and the pH maintained at about 8 via the addition of NaOH as needed. After 12 hours the solution was freeze-dried and the solid residue chromatographed (column) on silica gel eluting with Solvent System 5. The major yellow fraction was concentrated, dissolved in H₂O and freeze dried to give the desired product as a bright yellow powder (150 mg, 49 percent); MP = 230-235°C (dec), and further characterized by: ¹³C NMR (D₂O) 166.41, 165.60, 160.00, 119.91, 116.02, 113.85, 111.71, 104.59, 45.20, 44.50, 43.96, 36.43. Example 26 Preparation of 1-(2-hydroxy-5-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid. To an argon purged, aqueous solution (25 ml) of N-(2-hydroxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid (200 mg, 0.4 mmole) (prepared by the procedure of Example 25) was added PtO₂ (130 mg) followed by the introduction of H₂ (Parr hydrogenator). After total disappearance of yellow color, the solution was purged with argon and filtered. The aqueous solution was then freeze-dried to give the product as a tan solid (146 mg, 78 percent). Example 27 Preparation of α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris(R-methylacetic) acid, 1-isopropyl-4,7,10-trimethyl ester; (PN-DOTMA trimethylisopropyl ester). To a solution of 1.00 g (2.37 mmole) of α-[3-(4-nitrophenyl)propyl]-1,4,7,10-tetraazacyclododecane-1-acetic acid, 1-methyl ester (prepared by the procedure of Example P) in 35 ml dry acetonitrile was added 1.15 g (8.32 mmoles) of anhydrous potassium carbonate with vigorous stirring under nitrogen. Optically active α-benzene sulfonate of lactic acid methyl ester (1.79 g, 7.36 mmoles S:R=98.2) was added and the mixture was stirred at room temperature for 60 hours. TLC analysis indicated formation of new products (R f =0.71, Solvent System 2 for titled tetraesters and R f =0.89 for triester). The resulting solution with suspended carbonate salts was poured into 40 ml of chloroform and the precipitated inorganic salts were filtered. Solvent was removed from this filtrate and the crude orange oil was chromatographed twice on a 2.54 x 40.64 cm (1 in. x 16 in.) flash silica gel column using Solvent System 2 as the eluent to afford the titled product as a nonresolved mixture of tetraester diastereomers (1.00 g, 1.47 mmole, 62% yield) which were free of underalkylated products. ¹H NMR analysis of this material showed it to contain approximately 0.5 equivalents of unreacted benzene sulfonate derivative. The NMR spectra of this material were not coalescent at 60°C in chloroform: ¹H NMR (CDCl₃, 60°C) 7.9-8.1(m, 2H), 7.2-7.4(m, 2H), 5.06(m, 1H), 3.4-4.0(m, 9H), 1.7-3.4(m, 20H), 1.0-1.7(m, 15H); IR (CDCl₃) cm⁻¹ 2980, 2840, 1725, 1710 (ester carbonyl), 1590, 1510, 1440, 1340; Fast atom bombardment mass spectrum, m/e 702 [M+Na⁺]⁺, 687. Example 28 Preparation of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-[tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris-(R-methylacetic) acid, 1-isopropyl-4,7,10-trimethyl ester; (PA-DOTMA trimethylisopropyl ester). α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris-(R-methylacetic) acid, 1-isopropyl-4,7,10-trimethyl ester (950 mg, 1.40 mmoles uncorrected) (prepared by the procedure of Example 27), which contained unreacted α-[3-(4-nitrophenyl)propyl]-1,4,7,10-tetraazacyclododecane-1-acetic acid, 1-methyl ester, was dissolved in 10 ml of 30% aqueous methanol containing 1.00 g of 10% palladium on carbon catalyst under a nitrogen atmosphere. Excess hydrogen was purged through the solution for 7 hours. At this point, TLC inspection revealed formation of a strongly ninhydrin positive material (R f =0.62 Solvent System 2, R f =.71 for starting material). The methanolic catalyst slurry was filtered through celite and evaporation of solvent provided 800 mg of the crude title product as a clear oil which contained benzene sulfonic acid (R f =0.09 Solvent System 2) from the concomitant hydrogenolysis of the benzene sulfonate ester. The crude oil was chromatographed on a 2.54 x 20.32 cm (1 in. x 8 in.) flash silica gel column with 10% methanol in chloroform which eluted a light yellow band in the void volume. Solvent System 2 was then applied to elute the titled product (480 mg) in 52% yield as a mixture of unresolved diastereomers and geometric isomers. Three distinct ab quartets were observed in the aromatic region of the ¹H NMR: ¹H NMR (CDCl₃, 30°C) 6.63-8.0(m (quartets), 4H), 5.07(m, 1H, isopropyl methine H), 3.53-3.9(m, 13 H with four singlets at 3.85, 3.73, 3.69 and 3.56), 3.46(m, 1H), 3.25(broad t, 3H), 2-3.1(m, 14H), 1.0-2.0(m, 15H); ¹³C NMR (CDCl₃, 30°C) 177.3, 177, 176.4, 176.2, 175.9, 174.3, 172.9, 170.6, 145.3, 144.9, 130.8, 129.7, 129.3, 129.1, 128.8, 128.4, 127.5, 126.3, 115.2, 115.1, 114.9, 69.0, 68.4, 67.3, 61.6, 57.8, 57.4, 56.7, 56.5, 56.4, 52.9, 52.7, 52.1, 50.8, 50.7, 50.6, 47.3, 47.1, 47.0, 46.9, 46.5, 46.3, 46.1, 44.8, 44.5, 44.3, 34.1, 32.9, 32.5, 32.2, 31.8, 24.8, 22.2, 22.1, 22.0, 21.8, 21.6, 15.8, 14.9, 7.7, 7.5, 7.4, 7.1; IR (CDCl₃) cm⁻¹ 2960, 2840, 1720, 1510, 1450, 1375; Fast atom bombardment mass spectrum, m/e 672 [M+Na⁺]⁺, 686. Example 209 Preparation of α-▪2-(4-aminophenyl)ethyl▪-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris-(R-methylacetic) acid; (PA-DOTMA). The diastereomeric mixture of α-▪2-(4-aminophenyl)ethyl▪-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris-(R-methylacetic) acid, 1-isopropyl-4,7,10-trimethyl ester (400 mg, 0.59 mmoles) (prepared by the procedure of Example 28) was dissolved in 50 ml of 6N concentrated hydrochloric acid and refluxed for 30 hours. TLC analysis (Solvent System 1) indicated conversion of ester (R f =0.98 Solvent System 1) to two new spots (R f =0.6, high diastereomer and R f =0.54, low diastereomer Solvent System 1, both spots UV, ninhydrin, and iodine positive). Excess solvent was removed on a rotary evaporator and after drying, a mixture of crude diastereomers of the title product (403 mg) was obtained as the hydrochloride salt. Preparative separation of the two diastereomers of the title product was accomplished by applying 290 mg (0.51 mmole) of the crude salt to a 1 x 13 cm silica flash gel column which was eluted with Solvent System 8. The high R f diastereomer (119 mg, 0.21 mmole) was obtained in purer form than the low R f diastereomer (90 mg, 0.16 mmole) since high R f diastereomer eluted from the column first: ¹H NMR for high R f diastereomer: ¹H NMR (D₂O, 90°C, pD=7.5) 7.12(d, 2H), 6.80(d, 2H), 3.66(m, 1H), 3.57(broad t, 3H), 2-3.4(m, 19H), 1.89(m, 1H), 1.37(m, 1H), 1.15(d, 3H), 1.10(d, 3H), 1.06(d, 3H); ¹³C NMR (D₂O, 90°C, pD=7.5) 184.4, 184.2, 184.0, 183.3, 135.9, 132.6, 131.7, 119.1, 78.2, 69.0, 61.7, 61.5, 61.1, 57.4, 54.1, 49.7, 49.6, 48.2, 47.7, 47.2, 34.8, 33.8, 9.6, 9.1, 9.0; Fast atom bombardment mass spectrum, m/e 566 [M+H⁺]⁺, 588 [M+Na⁺]⁺, 604 [M+K⁺]⁺, 626 [M+K⁺+Na⁺-H⁺]⁺, 642 [M+2K⁺-H⁺]⁺. Preparation of Final Products - Complexes Metal ligand complexes were prepared by various methods as shown below. The methods included mixing of the metal and ligand in aqueous solution and adjusting the pH to the desired value. Complexation was done in solutions containing salts and/or buffers as well as water. Sometimes heated solutions were found to give higher complex yields than when the complexation was done at ambient temperatures. Also the work-up used in the synthesis of BFC has been shown to effect the complexation. Example 30 Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, ammonium salt, samarium(III) complex; Sm(BA-DOTA). A small sample, 53 mg, (0.094 mmole) of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (prepared by the procedure of Example 3) was dissolved in 100 µl of water and treated with 3 ml of 0.043M Sm(OAc)₃ solution (48.8 mg, 0.128 mmole) at pH 6-7. This solution was heated at 100°C and the degree of complexation was determined by anion exchange HPLC. When complexation was complete by anion exchange chromatography, HPLC System III, the solution of the complex was cooled to room temperature (about 25°C) and freeze dried. The samarium complex was purified by silica gel chromatography (eluting with Solvent System 1). This procedure gave the title product in 82 percent yield. This complex was characterized by TLC, fast atom bombardment mass spectrometry, anion exchange HPLC, and futher characterized by: ¹H (D₂O) 8.94, 7.81, 7.21, 6.97, 6.80, 5.63, 5.01, 4.58, 4.01, 3.56, 1.78, 1.53, 1.24, 1.10, 0.77, -2.80, -2.95, -3.21, -3.91; ¹³C NMR (D₂O) 190.3, 184.9, 181.4, 146.8, 134.3, 122.7, 116.4, 80.8, 72.6, 64.2, 57.2, 55.8, 54.7, 53.4, 51.5, 49.7, 45.5, 43.5, 23.6. Example 31 Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium(III) complex. A solution of 150 µl Sm-153 (3 x 10⁻⁴M, in 0.1N HCl) and 600 µl SmCl₃ (3 x 10⁻⁴M) in 0.1N HCl was prepared by adding the Sm-153 solution to the SmCl₃ solution. Then 5.0 µl of 2.0M NaOAc was added followed by 45 µl of 50 mM ligand (prepared by the procedure of Example 3) in HEPES buffer. The pH of the solution was adjusted to 7 with 275 µl of 0.5M HEPES. This solution was split into two fractions of 500 µls each, and one fraction was heated for 1 hour at 100°C. The solutions were passed through SP-Sephadex™ cation excange resin. The percent of metal as a complex was determined using the procedure previously described. The results showed 99.6% of the metal as a complex for the heated sample and 96.6% for the non-heated sample. Stability of chelates by pH profile. The stability of metal ligand complexes was measured by subjecting them to various pH values and analysing for complex in solution. At low pH, protonation of the ligand can cause the release of metal. At high pH, metal hydroxides compete with chelate formation. Thus, when looking for inert chelates, a desirable inert chelate will remain as a chelate when exposed to high and low pH values. Profiles of the inertness at various pH values for some of the chelates of this invention were generated using the methods described in the following examples. In some cases free metal was removed by passing the solution through a cation exchange resin. Dilute sodium hydroxide and hydrochloric acid solutions were used to adjust the pH of the complex solutions from 1 to 14. The percent metal as a complex was then determined by the methods previously described. In a similar manner, several bifunctional chelate conjugates were prepared and subjected to pH 2.8, 4 and 6. The amount of conjugate remaining in solution was determined by HPLC using a radiometric detector. The results are shown in Example XX in the biology section. Example 32 pH Stability of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium(III) complex. The heated and non-heated samples from Example 30 were each split into 2 x 250 µl aliquots. One 250 µl aliquot was adjusted with HCl to give the pH's represented in the table following. The second 250 µl aliquot was adjusted with µl quantities of NaOH to the desired pH's. Once the desired pH was reached, a 25 µl aliquot was removed and the percent of metal as complex determined as previously described. The results are as follows: pH % Complex Heated Not heated 1 98.9 92.7 3 99.6 93.3 5 99.6 92.9 7 99.6 95.7 9 99.9 95.8 11 99.6 95.7 13 99.6 94.5 Example 33 Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, yttrium(III) complex. Ten µl of a solution containing 1.4 mg/100 µl of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (prepared by the procedure of Example 3) was added to 100 µl of Y(OAc)₃ (0.003M) spiked with Y-90. To this solution was added 500 µl of water followed by 125 µl of NaOAc (0.5M). Water (265 µl) was added to the solution to bring the total volume to 1 ml. This solution was divided into two aliquots. One aliquot was heated to 100°C for 1 hour. Both heated and non-heated samples were tested to determine the percent of metal as a complex using the cation exchange procedure previously described. The results showed 84% and 4% of the metal as a complex for the heated sample and the non-heated sample, respectively. Example 34 Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, lutetium(III) complex. A solution of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (prepared by the procedure of Example 3) was dissolved in distilled water to yield a concentration of 1.63 mg/ml. A lutetium chloride solution was prepared by dissolving lutetium chloride in 0.1N HCl to result in a concentration of 3.9 mg/ml (0.01M). Lutetium-177 (0.3 mmolar) was used as a tracer. A volume of 30 µl of 0.01M lutetium solution was added to 2 µl of Lu-177 solution. The appropriate amount of ligand from above was added and HEPES buffer (0.1M, pH = 7.6) was added to give a total volume of 1.0 ml. The resultant solutions were 0.3 mmolar in ligand and lutetium. The solution was then heated to 100°C for one hour and the percent of Lu as a complex determined to be 86% by the cation exchange method described previously. Example 35 Preparation of α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium(III) complex. A sample, 7 mg, (10.8 µmole) of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium(III) complex (prepared by the procedure of Example 30) was dissolved in 400 µl water. Excess thiophosgene (50 µl) was added, followed by 400 µl CHCl₃ and the two-phase reaction stirred vigorously for 30 minutes. At the end of this time, the water layer was extracted with 500 µl CHCl₃ four times, and the water layer then was lyophilized to give the desired titled product in quantitative yield. The UV showed this compound to have a band at 272 and 282 nm. The TLC, silica gel developed by 75:25 V:V CH₃CN:H₂O, gave R f = 0.38. The starting material has an R f = 0.19. IR showed -SCN stretch at 2100 cm⁻¹; fast atom bombardment mass spectrum [M+H⁺]⁺ = 687. Example 36 Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, ammonium salt, yttrium(III) complex. A sample, 90 mg (160 mmole), of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (prepared by the procedure of Example 3) was dissolved in 1 ml water. To this solution was added 3 ml of water containing 51 mg (192 mmole) of Y(OAc)₃. The reaction mixture, pH = 6 to 7, was then heated at 100°C for two hours. The resulting solution was then passed through glass wool and lyophilized to give 126 mg of yellow solid. The solid was chromatographed on silica gel (Solvent System 1) to yield 71 mg (76 percent) of the desired complex product. Analysis by anion exchange showed the same retention time as was found for the analogous Sm complex. The title product was characterized by: ¹³C NMR (D₂O) 180.8, 180.5, 179.9, 146.1, 133.4, 122.0, 116.1, 74.9, 66.3, 56.3, 55.8,55.4, 55.1, 54.8, 52.2, 46.0, 44.0, 23.6; ¹H NMR (D₂O) 6.90(d), 6.70(d), 4.40(s), 3.45-3.06(m), 2.71-2.10(m), 1.75(s). Fast atom bombardment mass spectrum, [M + H⁺]⁺ = 582. Example 37 Preparation of α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, sodium salt, yttrium(III) complex. A sample of the α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, yttrium complex (prepared by the procedure of Example 36) (10 mg, 17 µmole) was dissolved in 400 µl H₂O. To this solution was added 64 µl thiophosgene (excess) and 400 µl CHCl₃ and the resulting mixture stirred vigorously for 40 minutes. During this time several small additions of solid NaHCO₃ were made to keep the pH at about 8. At the end of the reaction, the water layer was separated and extracted with 1 ml of CHCl₃, four times, and lyophilized. The title product was characterized by TLC and UV spectroscopy. Example 38 Preparation of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, yttrium(III) complex, ammonium salt; NH₄[Y(PA-DOTA)]. The ligand, α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (prepared by the procedure of Example 8) was converted to the mixed protonated-ammonium salt by chromatography on a strong cation exchange resin (SP-Sephadex™ C-25, Pharmacia). The column was in the protonated form and washed with distilled water. A concentrated aqueous solution of the ligand was applied to the column, followed by washing the column with distilled water. The ligand was eluted from the column with 0.5M NH₄OH. The eluent was reduced to dryness. A solution of Y(OAc)₃·4H₂O (0.0728 g, 0.215 mmole) in 5 ml of distilled water was added to a warm solution of the mixed protonated-ammonium salt ligand (0.120 g, 0.215 mmole) in 5 ml of water. The solution was brought to reflux and the pH adjusted to about 7.0 with 0.1M NH₄OH. After 1 hour at reflux, the solution was cooled and reduced to dryness. Excess NH₄OAc was removed by heating the white solid in an oil bath at about 105°C under vacuum. The title product (which contained about one equivalent of ammonium acetate) yield was 0.142 g (94 percent) and was characterized by: ¹³C NMR (D₂O, 88°C, 75 MHz) 23.8, 27.6, 35.4, 49.6, 55.0, 56.2, 56.9, 57.1, 65.7, 68.0, 121.7, 132.6, 138.8, 180.7, 181.4, 182.0, 183.1; Fast atom bombardment mass spectrum, m/e 610 (positive ion, [M⁻+2H⁺]⁺), 608 (negative ion, M⁻). Example 39 Preparation of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium(III) complex, ammonium salt; NH₄[Sm(PA-DOTA)]. When the procedure of Example 38 was repeated, using Sm(OAc)₃·3H₂O (0.082 g, 0.215 mmole) in place of Y(OAc)₃·4H₂O, the title product (which contained about one equivalent of ammonium acetate) was prepared in a yield of 0.155 g (94 percent) and was characterized by: ¹³C NMR (D₂O, 88°C, 75 MHz) 23.5, 27.2, 35.6, 50.5, 54.5, 56.0, 57.2, 57.9, 69.5, 71.5, 122.3, 133.0, 139.7, 181.2, 188.4, 189.3, 190.9; Fast atom bombardment mass spectrum, m/e 673 (positive ion, [M⁻+2H⁺]⁺, Sm isotope pattern), m/e 671 (negative ion, M⁻, Sm isotope pattern). Example 40 Preparation of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium(III) complex, ammonium salt; NH₄[Sm(SCN-PA-DOTA)]. Solutions of Sm(OAc)₃·3H₂O (27.9 mg, 381.56 g/mole, 73.1 µmole) in 10 ml of distilled water and 42 mg of PA-DOTA, mixed ammonium-potassium salt (632.97 g/mole, 66.4 µmole) (prepared by the procedure of Example 8) in 10 ml of distilled water were mixed and heated on a steam bath. After 30 min., the reaction to form [Sm(PA-DOTA)] was complete as determined by HPLC using the method described in Example 41. The solution was reacted with a solution of 45.4 mg of CSCl₂ (114.98 g/mole, 395 µmole) in 20 ml of chloroform by shaking in a separatory funnel. The reaction was complete after about one min. as determined by HPLC and by the absence of a positive test with ninhydrin (0.2 % in ethanol) when the aqueous solution was spotted on a silica gel TLC plate (the starting chelate, [Sm(PA-DOTA)], tested positive). The chloroform layer was removed and the aqueous layer was washed with two 20 ml portions of chloroform. The aqueous layer was reduced to dryness by the addition of 100 ml of acetonitrile and evaporated at ambient temperature under a stream of nitrogen to yield 56 mg of the title product. Fast atom bombardment mass spectrum, m/e 715 (positive ion, [M⁻+2H⁺]⁺, Sm isotope pattern), m/e 713 (negative ion, M⁻, Sm isotope pattern). Example 41 HPLC Analysis of the rate of chelation of Y³⁺ with PA-DOTA. The rate of PA-DOTA chelation with Y³⁺ was studied as a function of the work-up used in the synthesis of PA-DOTA. The extent of chelation was monitored by HPLC using an Alltech Econosphere™ C18 100 mm column. The gradient used was: A) 95:5 of pH 6.0, 0.05M NaOAc buffer:CH₃CN, B) 30:70 of pH 6.0, 0.05M NaOAc buffer:CH₃CN, A to B in 15 min. A solution of PA-DOTA·nHCl (retention time = 1.31 min) and of PA-DOTA mixed ammonium-potassium salt (retention time = 4.55 min), both prepared by the procedure of Example 8, were prepared as 1.6 mM, pH 6.0 0.5M NaOAc buffer. One ml (1.6 µmole) of each of the two solutions was reacted with 0.2 ml (8 µmole) of Y(OAc)₃·4H₂O solution (40 mM in pH 6.0 0.5M NaOAc buffer). Chelate formation was determined by the appearance of a peak at a retention time = 3.96 min (confirmed by comparison to a sample from Example 38). Chelate formation results were as follows. PA-DOTA Salt % Complex Time(min)/Temp. PA-DOTA·nHCl >90 <1/ room temp. PA-DOTA mixed ammonium-potassium salt <10 15/ room temp. >85 10/ 90°C Clearly, the method of purification of the BFC has an effect on the rate of chelation. Example 42 Preparation of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris(methylacetic) acid, samarium(III) complex, ammonium salt; NH₄[Sm(PA-DOTMA)]. A solution of Sm(OAc)₃·3H₂O (13.2 mg in 2 ml of distilled water) was added to a solution of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris-(methylacetic) acid (30 mg in 2 ml of distilled water), (prepared by the procedure of Example 29, high R f diastereomer). The pH 6.5 solution was heated on a steam bath and the reaction was monitored by HPLC. After 30 min. of heating the solution was reduced tom dryness on a rotary evaporator and dried in a vacuum oven. Fast atom bombardment mass spectrum, m/e 715 (positive ion, [M+2H⁺]⁺, Sm isotope pattern), 737 (positive ion, [M+H⁺+Na⁺]⁺, Sm isotope pattern) 713 (negative ion, (M⁻), Sm isotope pattern). In the following examples the complex solutions were passed through an ion exchange column to remove any excess free metal from solution. Labile systems would return to equilibrium and similiar amounts of the free metal would be in solution. Inert systems would not re-equilibrate and the amount of free metal should decrease. Thus even though a complex can be formed in low yield, a purification by passing it through an ion exchange resin could result in a usable stable complex without uncomplexed metal. Example 43 Preparation of α-(2-methoxy-5-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium(III) complex. A 3 x 10⁻²M solution of α-(2-methoxy-5-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (prepared by the procedure of Example 12) was prepared by dissolving 5.8 mg in 325 µl NANOpure™ water. A 10 µl aliquot of this solution was added to 990 µl of 3 x 10⁻⁴M SmCl₃ (in 0.1N HCl) spiked with Sm-153. The pH was then brought to 7.0 with NaOH. This solution was split into two fractions of 500 µl each, and one fraction was heated for 1 hour at 100°C. Both heated and non-heated samples were tested to determine the percent of metal as a complex by the cation exchange method described previously. The solution was then passed through SP-Sephadex™ resin. Complexation was again determined as the purified samples. The results are shown in the following table. Heated Non-Heated Purified Not Purified Purified Not Purified % Complex 96 95 97 89 Example 44 pH Stability of α-(2-methoxy-5-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium(III) complex. The heated and non-heated purified samples from Example 43 were each split into 2 x 250 µl aliquots. One aliquot was adjusted with HCl and the other with NaOH to give the pH's represented in the table following. After the desired pH was reached the sample was allowed to stand for 10 min and the amount of metal as a complex was determined by the cation exchange method described previously. The results are shown in the following table. pH % Complex Heated Not heated 2 95 94 3 97 95 5 98 97 7 96 97 9 98 96 11 97 98 13 100 99 Example 45 Preparation of α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium(III) complex. A 3 x 10⁻²M solution of α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (prepared by the procedure of Example 11) was prepared by dissolving 7.9 mg in 464 µl NANOpure™ water. A 10 µl aliquot of this solution was added to 950 µl of 3 x 10⁻⁴M SmCl₃ (in 0.1N HCl) spiked with Sm-153. The pH was then brought to 7.0 with NaOH. This solution was split into two fractions of 500 µl each, and one fraction was heated for 1 hour at 100°C. Both heated and non-heated samples were tested to determine the percent of metal as a complex using the cation exchange method described previously. The solutions were passed through SP-Sephadex™ resin. Complexation was then determined on the purified samples using the general procedure described hereinbefore. The results are shown in the following table. Heated Non-Heated Purified Not Purified Purified Not Purified % Complex 100 72 100 46 Example 46 pH Stability of α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, Sm(III) complex. The heated and non-heated purified sample from Example 45 were each divided into two aliquots. One aliquot was adjusted with dilute HCl and the other with NaOH to give the pH's represented in the table following. After the desired pH was reached the sample was allowed to stand for 10 min and the amount of metal as a complex was determined by the cation exchange method described previously. The results are shown in the following table: pH Purified Heat No heat 2 99 99 4 100 100 5 100 100 7 100 100 9 100 100 11 100 100 13 100 100 Example 47 Preparation of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, samarium(III) complex. A 0.0219M (100 µl, 2.195 mmole) solution of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (prepared by the procedure of Example 4) was contacted with a 0.043M (25 µl, 1.075 mmole) solution of Sm(OAc)₃. The reaction mixture was subjected to anion exchange HPLC (Q-Sepharose™ column, 1 cm x 25 cm, flow rate = 2 ml/min, eluted with 0-1M NH₄OAc gradient over 30 min). After one hour, the complex (retention time = 11.1 min) had formed in 77 percent yield (area percent) and was completely resolved from the ligand peak (retention time = 15.5 min). Additional evidence that the title complex had formed was obtained on silica gel TLC (Solvent System 4) whereby the ligand has an R f = 0.59 and the complex has an R f = 0.00. Example 48 Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, samarium(III) complex. A solution, 0.022M (100 µl, 2.2 µmole), of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (prepared by the procedure of Example 5) was contacted with a 0.043M (6.4 µl, 0.275 µmole) solution of Sm(OAc)₃. The reaction mixture was subjected to anion exchange HPLC (Q-Sepharose™ column, 1 cm X 25 cm, flow rate = 2 ml/min, eluted with 0-0.25M NH₄OAC gradient over 30 min). After forty minutes, the complex (retention time = 9.0 min) had formed in 66 percent yield (area percent) and was completely resolved from the ligand peak (retention time = 18.5 min). Example 49 Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, samarium(III) complex and α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,10-triacetic acid, sammarium(III) complex. A 3 x 10⁻²M solution of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid pentahydrochloride and α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,10-triacetic acid pentachloride (prepared by the procedure of Example 5) was prepared by dissolving 4.2 mg in 300 µl NANOpure™ water. A 10 µl aliquot of this solution was added to 15 µl of 2 x 10⁻²M SmCl₃ (in 0.1N HCl) spiked with Sm-153. The volume was brought to 1 ml by addition of water. The pH was then brought to 7.0 with NaOH. This solution was split into two fractions of 500 µl each, and one fraction was heated for 1 hour at 100°C. Both heated and non-heated samples were tested to determine the percent of metal as a complex by the cation exchange method described previously. The results showed 89% and 96% of the metal as a complex for the heated and non-heated samples, respectively. Example 50 pH Stability of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, samarium(III) complex, and α-(4aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,10-triacetic acid, samarium(III) complex. The heated sample from Example 49 and the non-heated sample were each divided into 2 aliquots. One aliquot was adjusted with HCl and the other with NaOH to give the pH's represented in the table following. Once the desired pH was reached, the samples were allowed to stand for 10 minutes and the percent of metal as complex was determined by the cation exchange method described previously. The results are shown in the following table: pH % Complex Heated Not heated 1 86 83 3 99 99 5 99 99 7 89 96 9 99 98 11 96 89 13 97 97 Example 51 Preparation of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, samarium(III) complex. Thirteen microliters of 2 x 10⁻²M solution of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (prepared by the procedure of Example 4) 15 µl of SmCl₃ (0.02M 0.1N HCl) and 2 µl of Sm-153, had the volume brought to 1 ml with NANOpure™ water. The pH was adjusted to 7.0 with NaOH. This solution was split into two fractions of 500 µl each, and one fraction was heated for 1 hour at 100°C. Both heated and non-heated samples were tested to determine the percent of metal as a complex using the cation exchange procedure described previously. The results showed 74% and 42% of the metal as a complex for the heated and non-heated samples, respectively. Example 52 pH Stability of α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, samarium(III) complex. The heated sample of Example 51 was divided into 2 aliquots. One aliquot was adjusted with HCl and the other with NaOH to give the pH values represented in the following table. After the desired pH was reached the sample was allowed to stand for 10 minutes and the amount of metal as a complex was determined by the cation exchange method described previously. The results are shown in the following table. pH % Complex 1 67 2 70 4 70 5 72 7 74 9 76 10 76 12 75 13 76 Example 53 Preparation of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, lutetium(III) complex. A solution of EA-DO3A (prepared by the procedure of Example 17) was made by dissolving the solid in water. The final concentration was 0.01M. A lutetium chloride solution was prepared by dissolving lutetium chloride in 0.1N HCl. The resultant concentration was 3.9 mg/ml of lutetium chloride (0.01M Lu). Lutetium-177 was used as the tracer. A volume of 30 µl of 0.01M Lu solution was added to 2 µl of Lu-177 solution. A volume of 30 µl of ligand was added and HEPES buffer (0.1M, pH = 7.6) was added to give a total volume of 1.0 ml. The resultant solution was 0.3 mM in ligand and lutetium. The amount of Lu as a complex was determined to be 98 percent by the cation exchange method previously described. Example 54 Preparation of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacylcododecane-4,7,10-triacetic acid, yttrium (III) complex; [Y(EA-DO3A)] The ligand, 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid (prepared by the procedure of Example 17) was converted to the mixed protonated-ammonium salt by chromatography on a strong cation exchange resin (SP-Sephadex™ C-25, Pharmacia). The column was in the protonated form and washed with distilled water. A concentrated aqueous solution of the ligand was applied to the column, followed by washing the column with distilled water. The ligand was eluted from the column with 0.5M NH₄OH. The eluate was reduced to dryness on a rotary evaporator and dried in a vacuum oven. A solution of Y(OAc)₃·4H₂O (0.203 g, 338.101 g/mole, 0.600 mmole) in 10 ml of distilled water was added to a warm solution of the mixed protonated-ammonium salt ligand (0.300 g, 499.615 g/mole, 0.600 mmole) in 10 ml of distilled water. The solution was brought to reflux and the pH was adjusted to about 7.0 with 0.1M NH₄OH. After 15 minutes at reflux, the solution was cooled and reduced to dryness on a rotary evaporator. Excess ammonium acetate was removed by heating the white solid in an oil bath at about 105°C under vacuum. The title product (which contained about one equivalent of ammonium acetate) was provided in a yield of 373 mg (99 percent) and was characterized by: ¹³C NMR (88°C, D₂O, 75 MHz) 24.4, 28.4, 51.2, 56.5, 57.2 (2C), 57.7, 67.2, 67.6, 120.5, 132.3, 135.2, 182.1, 182.5, 183.0; Fast atom bombardment mass spectrum, m/e 552 (positive ion, [M+H⁺]⁺), m/e 610 (negative ion, [M+OAc⁻]⁻). Example 55 Preparation of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium complex; [Sm(EA-DO3A)]. When the procedure of Example 54 was repeated, using Sm(OAc)₃·3H₂O (0.229 g, 381.531 g/mole, 0.600 mmole) in place of the Y(OAc)₃·4H₂O, the title product (which contained about one equivalent of ammonium acetate) was prepared in a yield of 408 mg (99 percent) and was characterized by: ¹³C NMR (88°C, D₂O, 75 MHz) 23.8, 27.9, 51.4, 57.5, 58.1 (3C), 68.7. 73.4, 120.3, 132.2, 134.7, 185.0, 186.8, 192.1; Fast atom bombardment mass spectrum, m/e 615 (positive ion [M+H⁺]⁺, Sm isotope pattern), m/e 673 (negative ion, [M+OAc⁻]⁻, Sm isotope pattern). Example 56 Preparation of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium(III) complex. Ten microliters of 1.48 mg/100 µl (0.03M) solution of 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-tetraacetic acid (prepared by the procedure of Example 20) was added to 15 µl of SmCl₃ solution (0.02M in 0.1N HCl) and spiked with Sm-153. The volume was brought to 1 ml with NANOpure™ water. This solution was divided into two 500 µl fractions, and one fraction was heated for 1 hour at 100°C. Both heated and non-heated samples were tested to determine the percent of metal as a complex using the cation exchange procedure described hereinbefore. The results showed 81% and 43% of the metal as a complex for the heated and non-heated samples, respectively. Example 57 pH Stability 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium(III) complex. The heated sample of Example 56 was divided into two aliquots. One aliquot was adjusted with HCl and the other with NaOH to give the pH's represented in the following table. After the desired pH was reached the sample was allowed to stand for 10 min and the amount of metal as a complex was determined by the cation exchange method described previously. The results are shown in the following table. pH % Complex 1 20 2 37 4 49 5 58 7 81 9 62 10 64 12 64 13 54 Example 58 Preparation of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium(III) complex. Three µl of 4.65 mg/100 ml solution of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid (prepared by the procedure of Example 20) was added to a solution of 15 µl of SmCl₃ (0.02M in 0.1N HCl) previously spiked with Sm-153. The volume was brought to 1 ml with NANOpure™ water. The pH of the solution was adjusted to 7.3 using NaOH. The solution was divided into two aliquots, and one aliquot was heated at 100°C for 1 hour. Both heated and non-heated samples were tested to determine the percent of metal as a complex by the cation exchange method described previously. The results showed 96% and 93% of the metal as a complex for the heated and non-heated samples, respectivly. Example 59 pH Stability of 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium(III) complex. The heated and non-heated samples of Example 58 were each divided into two aliquots. One aliquot of each sample was adjusted with HCl and the other with NaOH to give the pH's shown in the following table. After the desired pH was reached, the sample was allowed to stand for 10 minutes and the amount of metal as a complex was determined by the cation exchange method described previously. The results are shown in the following table. pH % Complex Heated Not Heated 1 44 13 3 50 42 5 73 55 7 96 93 9 98 98 11 89 90 13 28 37 Example 60 Preparation of 1-(2-hydroxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium(III) complex. A 3 x 10⁻²M solution of 1-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid (prepared by the procedure of Example 25) was prepared by dissolving 3.9 mg in 260 µl NANOpure™ water. A 10 µl aliquot of this solution was added to 15 µl of 2 x 10⁻²M SmCl₃ (in H₂O) spiked with 10 µl of Sm-153 in 0.1N HCl (3 x 10⁻⁴M). The volume was brought to one milliliter by addition of 965 µl DI H₂O. The pH was then brought to 7.0 with NaOH. This solution was split into two fractions of 500 µl each, and one fraction was heated for 1 hour at 100°C. Both heated and non-heated samples were tested to determine the percent of metal as a complex by the previously described cation exchange method. The results showed 71 percent and 74 percent of the metal as a complex for the heated and non-heated samples, respectively. Example 61 pH Stability of 1-(2-hydroxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium(III) complex. The heated and non-heated sample of Example 60 were each split into two 250 µl aliquots. One aliquot was adjusted with HCl and the other with NaOH to give the pH's represented in the table following. After the desired pH was reached the sample was allowed to stand for 10 minutes and the amount of metal as a complex was determined by the cation exchange method described previously. The results are shown in the following table. pH % Complex Heated Not heated 1 65 51 3 98 93 5 99 99 7 100 100 9 100 99 11 100 96 13 100 98 Example 62 Preparation of 1-(2-hydroxy-5-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium(III) complex. A 3 x 10⁻²M solution of 1-(2-hydroxy-5-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid (prepared by the procedure of Example 26) was prepared by dissolving 3.2 mg in 100 µl NANOpure™ water. A 10 µl aliquot of this solution (diluted to 20 µl) was added to 15 µl of 2 x 10⁻²M SmCl₃ (in H₂O) spiked with Sm-153. The volume was brought to 1 ml by addition of 950 µl DI H₂O and 20 µl 0.1N NaOH. This solution was split into two fractions of 500 µl each, and one fraction was heated for 1 hour at 100°C. Both heated and non-heated samples, were tested to determine the percent of metal as a complex by the cation exchange method described previously. When less than 95 percent of the metal was complexed, the solution was passed through SP-Sephadex™ resin. The percent of metal as a complex was again determined. The results are shown in the following table. Heated Non-Heated Purified Not Purified Purified Not Purified % Complex 99 68 99 21 Example 63 pH Stability of 1-(2-hydroxy-5-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium(III) complex. The heated and non-heated purified chromatographed samples from Example 62 were each split into two 250 µl aliquots. One 250 µl aliquot was adjusted with HCl and the other with NaOH to give the pH's represented in the table following. Once the desired pH was reached, samples were allowed to stand for 10 minutes and the percent of metal as complex was determined by the cation exchange method described previously. The results are as shown in the following table: pH % Complex Heated Not heated 1 60 56 2 74 76 3 84 87 5 97 98 7 99 99 9 99 98 11 99 99 13 99 99 Methods of Use-Biology Bifunctional chelants having within the same molecule a metal chelating group such as DTPA and a reactive linker (the aryl amine) are known to be capable of being covalently attached to various target directed biomolecules having specificity for cancer or tumor cell epitopes or antigens. Radionuclide complexes of such conjugates are useful in diagnostic and/or therapeutic applications as means of conveying the radionuclide to a cancer or tumor cell. [Reference, Meares et al., Anal. Biochem. 142 , 68-78 (1984); see also discussion on pp. 215-216 of J. Protein Chem., 3 (2) (1984) by Meares and Goodwin, more recent references are Meares, U.S. Patent 4,678,677, issued July, 7, 1987, Warshawsky et al. U.S. Patent 4,652,519, issued March 24, 1987 and Brechbiel, et al., Inorg. Chem., 25 , 2772-2781 (1986)]. Conceivably, the product, employing radioactive or luminescent metals, may also be used for in vitro immunoassays. Background Information The utility of the labeled antibodies depends on a number of factors, for example: 1) the specificity of the antibody, 2) the inertness or stability of the complex under use conditions (i.e., serum stability), and 3) the labeling technique such that the integrity of the antibody may have the same specificity and immunoreactivity as that of the native molecule. Stability or inertness of the complex is of utmost importance to the effectiveness of the radionuclide-antibody conjugate as a diagnostic and/or therapeutic agent. Kinetic lability can lead to instability, e.g. in the serum, and the dissociation of the radionuclide from the complex. Thus it diminishes the diagnostic and therapeutic effectiveness. In addition, it poses a greater potential for general radiation damage to normal tissue. [Cole, et al., J. Nucl. Med., 28 , 83-90 (1987)]. Linking of Radionuclide to Antibody Attachment of radionuclide to antibody can be carried out by either linking the BFC to the antibody via procedures well known in the art, followed by chelation of the radionuclide under conditions compatible with the antibody, or alternatively, conjugation of the antibody to preformed (ambient or elevated temperature) metal - BFC complex. [Meares et al. Acc. Chem. Res. 17 , 202-209 (1984)]. Examples are provided for the latter. Example ZA (Comparative) Conjugation of 1-(4-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid, samarium-153 complex to IgG and F(ab′)₂ of CC-49; [¹⁵³Sm(SCN-Bz-DTPA)]-IgG and [¹⁵³Sm(SCN-Bz-DTPA)]-F(ab′)₂ fragment. The 1-(4-isothiocyanotobenzyl)diethylenetriaminepentaacetic acid, samarium-153 complex [¹⁵³Sm(SCN-Bz-DTPA)] was prepared by mixing 150 µl ¹⁵³Sm in 0.1N HCl with 9 µl of 1-(4-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid to which was added HEPES buffer (0.5M pH 8.9, approximately 30 µl) to bring the pH to about 6. To conjugate, 22.5 x 10⁻⁹ moles of IgG or F(ab′)₂ of CC-49 (about 1 x 10⁻⁴M concentration of protein in 50 mmole HEPES, pH 8.5) was mixed with the ¹⁵³Sm complex, and the pH was adjusted to 8.9 by addition of a sodium carbonate solution (1.0M, 12-15 µl). Conjugation was carried out at room temperature (about 25°C) for about 3 hours. The ¹⁵³Sm complex labeled IgG or F(ab′)₂ was isolated and characterized similarly as described in Example XII. Experimental for Biology Examples I, & II and Comparative Examples A-D IN VIVO SCREENING OF BIFUNCTIONAL CHELATES . The stability of certain rare earth chelates has been examined by in vivo testing in animals. For example, Rosoff, et al. in the International Journal of Applied Radiation and Isotopes 14 , 129-135 (1963) report on the distribution of radioactive rare earth chelates in mice for certain aminocarboxylic acids. It was found that in vivo "the competition between the chelating agent and body constituents (inorganic and organic) for the rare-earth ion, determines its deposition and excretion." The strong rare-earth chelates are believed to dissociate very little and be excreted, while the weak and intermediate strength chelates dissociate more readily and thus are deposited in organs such as the liver. However, concentration of radionuclide in the liver is not always due to weak complex formation, but in some cases is due to the affinity that the metal chelate has for the liver. Chelates have, in fact, been prepared and utilized for the evaluation of liver function [Fritzberg, Alan R., Radiopharmaceuticals: Progress and Clinical Perspectives , Vol. 1, 1986; U.S. Patents 4,088,747 and 4,091,088]. The biodistribution of the yttrium and samarium chelates of the compound of Example 3 were determined and the percent dose in the liver was used as an in vivo screening procedure to qualitatively estimate the stability of the chelates. Chelates of NTA and EDTA are included for comparison. Also samarium was injected as samarium chloride in unchelated form as a control. Sprague-Dawley rats weighing from 150 to 200 g were purchased from Charles River Laboratories. These animals were placed in cages and fed water and food ad libitum . The animals were acclimated for at least five days before use. Prior to injection of complex, the animals were placed under a heat lamp (15 to 30 minutes) to dilate the tail vein. The animal was then placed in a restraining cage, the tail cleaned with an alcohol swipe, and the animal injected (50 to 200 µl) via the tail vein. After injection, the animal was placed in another cage for two hours after which time the animal was sacrificed by cervical dislocation. The animal was then dissected, the parts rinsed with deionized H₂O, patted dry, and weighed into a tared counting vial. At least three standards of the same material as injected were prepared and counted with the animal tissues. Percent of dose is the number of counts in the organ divided by the number of counts in the standard multiplied by 100 (see the following Table). Biodistribution Data Example No. Ligand of Ex. Metal % Injected Dose in Liver I 3 Y 0.17 II 3 Sm 0.29 (A) EDTA Sm 8.4 (B) EDTA Sm 4.4 (C) NTA Sm 8.6 (D) SmCl₃ Sm 39 Examples III and E. The 1:1 complexes of yttrium (spiked with a tracer amount of ⁹⁰Y) with the ligand of Example 3, which is BA-DOTA, and EDTA (Comparative E) were prepared by methods described previously. Several 100 µL aliquots were then transferred to separate centrifuge tubes. Excess Y(III) was added such that the total volume change is minimized and the time noted. One-half hour after metal addition, the percent complex was determined by the cation exchange method described previously and this was compared to the original amount of complex. The percent complex versus added metal gives an indication as to the lability of the ligand-metal complex. The results are given in the Table. Complex Study Metal/Ligand Molar Ratio % Complex BA-DOTA EDTA 1 80 98 10 -- 86 100 -- 78 250 88 48 500 80 16 Example IV Preparation of 1-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium-153 complex; [¹⁵³Sm(SCN-EA-DO3A)] complex. To 100 µl of ¹⁵³Sm in 0.1N HCl was added 5 µl of SCN-EA-DO3A (5mM in 50 mM HEPES, pH 8.2) (prepared in Example 18). This was mixed on a vortex mixer, and HEPES buffer (0.5M, pH 8.9) was added gradually (about 25 µl total) to adjust the pH to around 7. The progress of the chelation was monitored by HPLC on GF-250 column (HPLC System I). Yields around 50% were obtained. Example V Preparation of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex; [¹⁵³Sm(PA-DOTA)] complex. To 150 microliters (µl) of ¹⁵³Sm solution in 0.1N HCl (approximately 4.6 mCi) were added 1 µl of sodium acetate (2.0M) and 9 µl of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mixed ammonium, potassium salt (5 mmole in 50 mmole HEPES, pH 8.5, prepared by the procedure of Example 8). The mixture was mechanically shaken and titrated gradually with a HEPES buffer (0.5M, pH 8.9; approximately 31 µl added) to pH 7. This was then heated at 98°C in a sand bath for 1 hour. Upon termination, 5 µl of the mixture was used for analysis on a Mono-Q™ column on HPLC System II, eluted with a gradient solvent system (0-15 minutes, from 0 to 100% B; where A = water, and B = 1.0M ammonium acetate and 0.1 mmole EDTA). Yields of 85-95% based on ¹⁵³Sm were obtained. The α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex thus prepared was characterized by comparison with the identical non-radioactive sample, by their respective chromatographic behavior on Mono-Q™ and GF-250 columns. Further evidence of the presence of the radioactive complex was determined by the conversion to the isothiocyanato derivative and its subsequent conjugation to antibody. The complex has also been prepared without heating (at ambient temperature) by incubation for 6 to 18 hours to result in 70-80% yield. Example VI Preparation of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7-10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex; [¹⁵³Sm(SCN-PA-DOTA)] complex. To the reaction mixture obtained in Example V was added 2 µl of HEPES buffer (0.5M, pH 8.9), 2 µl of thiophosgene and 0.2 ml of chloroform. The mixture was mechanically shaken vigorously 2 or 3 times for a few seconds each time. The chloroform layer was discarded and the aqueous layer which contained mainly the desired product was saved and further purified. The yield of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7-10-tetraazacyclo dodecane-1,4,7,10-tetraacetic acid, samarium-153 complex, based on ¹⁵³Sm activity measurement by HPLC on GF-250 column using HPLC System I, was 85-90%. To purify, the aqueous layer was passed through a Sep-Pak™ C-18 cartridge and eluted with 90% acetonitrile in water. The first 300 µl of effluent was discarded, and the SCN-derivative which came off in the next 900 µl was characterized by HPLC on GF-250. The recovery of the ¹⁵³Sm activity was better than 90%. The bulk of the solvent was then evaporated over a period of 1.5 to 2 hours, and the residue was used for conjugation to antibody. Example VII Preparation of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex; [¹⁵³Sm (BA-DOTA)] complex. To 200 µl of ¹⁵³Sm solution in 0.1N HCl were added 1 µl of sodium acetate (2.0M) and 12 µl of α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (5 mmole in 50 mmole HEPES, pH 8.5) (prepared by the procedure of Example 3). The mixture was mechanically shaken and titrated gradually with a HEPES buffer (0.5M, pH 8.9; approximately 38 µl added) to pH 7. This was then heated at 98°C in a sand bath for 1 hour. Upon termination, 5 µl of the mixture was used for analysis on a Mono-Q™ column (HPLC System II, eluted with a gradient solvent system: 0-15 minutes, from 0 to 100% B; where A = water, and B = 1.0M ammonium acetate and 0.1 mmole EDTA). In general, yields of 85-95% based on ¹⁵³Sm were obtained. The complex has also been prepared by incubation of the mixture at room temperature for 12-18 hours which resulted in a yield of the title product of 80-90%. The α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex thus prepared was characterized by comparison with an authentic sample by their chromatographic behavior on the Mono-Q™ column, conversion to the isothiocyanato derivative and its subsequent conjugation to antibody. Example VIII Preparation of α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex; [¹⁵³Sm(SCN-BA-DOTA)] complex. To the reaction mixture obtained in Example VII were added 2 µl of HEPES buffer (0.5M, pH 8.9), 2 µl of thiophosgene and 0.2 ml of chloroform. It was mechanically shaken vigorously 2 or 3 times for a few seconds each time. The chloroform layer was discarded and the aqueous layer which contained mainly the desired product was saved and further purified. The yield of α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex, as analyzed by HPLC on GF-250 column based on the ¹⁵³Sm activity using the HPLC System I was over 90%. To purify, the aqueous layer was passed through a Sep-Pak™ C-18 cartridge and eluted with 90 percent acetonitrile in water. The first 0.3 ml of effluent was discarded, and the desired product came off in the next 1.2 ml, with 86-93% recovery. The bulk of the solvent was then evaporated over a period of about 2 hours, and the residue was used for conjugation to antibody. Example IX Conjugation of 1-[2-(4-isothiocyantophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samariuim-153 complex to antibody; [¹⁵³Sm(SCN-EA-DO3A)]-IgG conjugate. The antibody used was CC-49, a murine monoclonal IgG that binds to an epitope of TAG-72, a tumor associated antigen. To conjugate, 187 µl of the antibody solution (1.20 x 10⁻⁴M in 50 mM HEPES, pH 8.5) was mixed with 4.5 x 10⁻⁸ moles of ¹⁵³Sm(SCN-EA-DO3A) prepared as described in Example IV followed by addition of a sodium carbonate solution (1.0M) to raise the pH to 8.9. The reaction was allowed to continue for 2 hours at room temperature. Upon termination, the ¹⁵³Sm labeled IgG was isolated by centrifugal gel filtration on Sephadex G-25 (2.2 ml) disposable columns, and further purified by HPLC on GF-250 column, eluted with a citrate buffer (0.25M, pH 7.4). The fractions contained the labeled IgG were pooled, concentrated and exchanged (3x) into PBS by use of Centricon™ concentrators. The specific activity of ¹⁵³Sm labeled IgG thus prepared was about 0.16 µCi/µg of protein. The integrity of the [¹⁵³Sm(EA-DO3A)]-IgG preparation was verified by HPLC (Sivakoff, S.I., BioChrom. 1 (1), 42-48 (1986)] and standard biochemical procedures, e.g. sodium dodecyl sulfate:polyacrylamide gel electrophoresis and autoradiography, and solid phase radioimmunoassay (RIA). [See David Colcher et al., Cancer Res. 43 , 736-742 (1983).] Example X Conjugation of 1-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, samarium-153 complex to Fragment F(ab′)₂ of CC-49; [¹⁵³Sm(SCN-EA-DO3A)]-Fragment F(ab′)₂ of CC-49. The F(ab′)₂ fragment of CC-49, prepared by enzymatic digestion according to the procedure described by Lamoyi and Nisonoff [E. Lamoyi and A Nisonoff, J. Immunol. Methods, 56 , 235-243 (1983)], (225 µl of 1 x 10⁻⁴M in 50 mM HEPES, pH 8.5) was mixed with 2.9 x 10⁻⁸ moles of ¹⁵³Sm(SCN-EA-DO3A) prepared as described in Example IV. Sodium carbonate (1.0M, about 5 µl) was added to bring the pH to 8.9, and the reaction was continued for about 2.5 hours. Upon termination, the ¹⁵³Sm labeled fragment was isolated and characterized as described in Example IX. Example XI (A and B) In vivo localization of [¹⁵³Sm(EA-DO3A)]-IgG and [¹⁵³Sm(EA-DO3A)]-F(ab′)₂. The utility of the ¹⁵³Sm(EA-DO3A) labeled IgG (from Example IX) and F(ab′)₂ of CC-49 (from Example X) was demonstrated by the uptake of the labeled materials by human tumor xenograft in athymic mice. Thus female athymic (Nu/Nu, CD1 background) mice were inoculated subcutaneously (S.C.) (0.1 ml/source) with the human colon carcinoma cell line, LS-174 T (approximately 1 x 10⁶ cells/animal). Approximately 2 weeks after inoculation, each animal was injected via the tail vein with about 2 µCi (15-30 µg) of ¹⁵³Sm labeled antibody in PBS. The mice were sacrificed at various time intervals. After exsanguination, the tumor and selected tissues were excised and weighed, and radioactivity was measured in a gamma counter. The counts per minute (CPM) of ¹⁵³Sm in each tissue was determined and expressed as CPM per gram of tissue per injected dose multiplied by 100 (% injected dose/gram). Results are shown in Figures 1-14 and Tables IA and IB. The ¹⁵³Sm(SCN-Bz-DTPA) labeled IgG and F(ab′)2 of CC-49 (from Example ZA) were included in the study for comparison. Results are shown in Table IC and ID. Example XII Conjugation of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7-10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex to antibody; [¹⁵³Sm(SCN-PA-DOTA)]-IgG conjugate. The antibody used was CC-49, a murine monoclonal IgG that binds to an epitope of TAG-72, a tumor associated antigen. To conjugate, 178 µl of the antibody solution (1.26 x 10⁻⁴M in 50 mmole HEPES, pH 8.5) was mixed with 3.4 x 10⁻⁸ moles of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,-10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium complex (prepared as described in Example VI), followed by addition of a sodium carbonate solution (1.0M, about 17 µl) to raise the pH to about 8.9. The reaction was allowed to continue for 2 hours at room temperature. Upon termination, the ¹⁵³Sm labeled IgG was isolated by centrifugal gel filtration on Sephadex™ G-25 (2.2 ml) disposable columns, and further purified by HPLC on GF-250 column, eluted with a citrate buffer (0.25M, pH 7.4). The fractions which contained the labeled IgG were pooled, concentrated and exchanged (3 times) into PBS by use of Centricon™ concentrators. The specific activity of the ¹⁵³Sm labeled IgG thus prepared was about 0.16 µci/µg of protein. The homogeneity and integrity of the α-[2-(4-isothiocyanatophenyl)-ethyl]-1,4,7,10-tetraazacyclo dodecane-1,4,7-10-tetraacetic acid, samarium-153 complex-IgG preparation was verified by HPLC and standard biochemical procedures as Example IX. The following Example is an alternative for making labeled antibody conjugates, which involves first conjugation of the BFC to the antibody, and the subsequent chelation to yield the radionuclide-BFC labeled Ab. Example XIIA Preparation of α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid - Ab CC₄₉ conjugate (IgG CC₄₉-PA-DOTA); and the sebsequent chelation with ¹⁵³Sm to form ¹⁵³Sm-labeled antibody (IgG CC₄₉-PA-DOTA-¹⁵³Sm). The ¹⁵³Sm(PA-DOTA) labeled antibody can be prepared by first coupling the BFC, e.g. α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (SCN-PA-DOTA), to an antibody at pH 8-9, followed by chelation with ¹⁵³Sm at pH 6 at room temperature for several hours. In a typical experiment, CC-49 was concentrated and exchanged three times into a carbonate buffer (50 mM, pH 9.1) in an Amicon Concentrator (30 K molecular weight cut off) to leave a solution with antibody concentration greater than 1.5 x 10⁻⁴M. To the formed conjugate was added 161 µl of the antibody solution containing 25 x 10⁻⁹ mole of IgG CC-49 mixed with 5 µl of the SCN-PA-DOTA (5mM concentration in the same carbonate buffer, prepared by the procedure of Example 18). The mixture was allowed to stand at room temperature for 5 hours, and terminated by filtration through the 30 K membrane in the Amicon Concentrator at 5000 rpm on the Sorvall RT centrifuge. The concentrate was further washed with 2 ml of a 0.25M DTPA solution in PBS at pH 7.4 and five times (2 ml each time) with MES buffer (20 mM, pH 5.8); centrifuged for 30 min. at each wash. At the end, the PA-DOTA-IgG conjugate was concentrated to a minimum volume (about 100 µl) and its integrity confirmed by HPLC analysis on a GF-250 column. To the purified conjugate was added a mixture of ¹⁵³Sm in 0.1N HCl (50 µl) and 20 µl of a MES buffer (1.0M, pH 6), mixed on a vortex mixer, and allowed to stand at room temperature overnight. Upon termination, the amount of ¹⁵³Sm incorporated, estimated by HPLC analysis, was 0.22 BFC-Sm/antibody. That ¹⁵³Sm was associated with the antibody through chelation with the BFC, which was linked covalently to the antibody, and not due to non-specific binding was demonistrated by the control experiment. In the control experiment, IgG CC-49 solution which was mixed with ¹⁵³Sm mixture under identical conditions, and isolated according to the same procedure, showed no appreciable amount of ¹⁵³Sm associated with it. Example XIII Conjugation of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex to fragment F(ab′)₂ of CC-49; [¹⁵³Sm(SCN-PA-DOTA)]-F(ab′)₂ fragment. The F(ab′)₂ fragment of CC-49 [prepared by enzymatic digestion according to the procedure described by (E. Lamoyi et al., J. Immunol. Methods 56 , 235-243 (1983)], (225 µl of 1 x 10⁻⁴M in 50 mmole HEPES, pH 8.5) was mixed with 2.9 x 10⁻⁸ moles of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex prepared as described in Example VI. Sodium carbonate (1.0M, about 9 µl) was added to bring the pH to around 8.9, and the reaction was continued for about 2.5 hours. The ¹⁵³Sm labeled fragment was isolated and characterized as described in Example IX. The specific activity was around 0.4 µCi/µg. Example XIV(A and B) In vivo localization of the conjugate of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex labeled IgG and F(ab′)₂; [¹⁵³Sm(SCN-PA-DOTA]-IgG and [¹⁵³Sm(SCN-PA-DOTA)]-F(ab′)₂. The utility of the conjugate of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex labeled IgG and F(ab′)₂ of CC-49 (from Example XII and XIII) was demonstrated by the uptake of the labeled materials by human tumor xenograft in athymic mice. The biolocalization was determined using the procedure described in Example XI. Results are shown in Figures 1 to 7 for IgG and Figures 8 to 14 for F(ab′)₂, also Tables IIA and IIB. The conjugate of ¹⁵³Sm(SCN-Bz-DTPA) with IgG and F(ab′)₂ labeled materials (prepared from Example ZA) were included in the study for comparison. (See Tables IC and ID.) Example XV Conjugation of α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex to Antibody; [¹⁵³Sm(SCN-BA-DOTA)]-IgG. Whole IgG of CC-49 (174 µl of 1.2 x 10⁻⁴M in 0.25M HEPES, pH 8.7) was mixed with 2.0 x 10⁻⁸ moles of α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 (2.8 mCi) prepared per Example VIII, followed by addition of a sodium carbonate solution (1.0M, about 2 µl) to maintain the pH about 8.7. The reaction was allowed to continue for 2.5 hours at room temperature. Upon termination, the ¹⁵³Sm labeled IgG was isolated by centrifugal gel filtration on Sephadex™ G-25 (2.2 ml) disposable columns, and further purified by HPLC on GF-250 column, eluted with a citrate buffer (.025M, pH 7.4). The fractions which contained the labeled IgG were pooled, concentrated and exchanged (3 times) into PBS by use of Centricon™ concentrators. Homogeneity and integrity of the samarium-153 labled IgG preparation was verified by HPLC and standard biochemical procedures as described in Example IX. Example XVI Conjugation of α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex to Fragment F(ab′)₂ of CC-49; [¹⁵³Sm(SCN-BA-DOTA)]-fragment F(ab′)₂ of CC-49. The F(ab′)₂ of CC-49 (84 µl of 2.4 x 10⁻⁴M in 0.25M HEPES buffer, pH 8.7), prepared by enzymatic digestion according to the procedure described by Lamoyi et al. was mixed with 2.1 x 10⁻⁸ moles of α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid, samarium-153 complex (prepared by the procedure of Example VIII). Sodium carbonate (1.0M, about 2 µl) was added to bring the pH to 8.7, and the reaction was continued for about 2 hours. Upon termination, the ¹⁵³Sm labeled fragment was isolated and characterized as described in Example XII. Example XVII (A and B) In vivo localization of α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex labeled IgG (Example XV) and F(ab′)2 (Example XVI); [¹⁵³Sm(BA-DOTA)]-IgG and [¹⁵³Sm(BA-DOTA]-F(ab′)₂. The in vivo study was conducted according to the protocol described in Example XIV or XI, and results are shown in Figures 1 to 14 and Tables IIIA and IIIB. Example XVIII (A and B) In vivo localization of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid ¹⁷⁷Lu-complex labeled IgG and F(ab′)₂; [¹⁷⁷Lu(PA-DOTA)]-IgG and [¹⁷⁷Lu(PA-DOTA)]-F(ab′)₂. The title compounds were prepared and in vivo studies were conducted according to protocol described in Examples V, VI, XII and XIII and results are shown in Tables IVA and IVB. Example XIX (A and B) In vivo localization of α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, yttrium-90 complex labeled IgG and F(ab′)₂; [⁹⁰Y(PA-DOTA)]-IgG and [⁹⁰Y(PA-DOTA)]-F(ab′)₂. The titled compounds were prepared and in vivo studies were conducted according to protocol described in Example V, VI, XII and XIII and results are shown in Tables VA and VB. Example XX In vitro pH stability of [¹⁵³Sm(BFC)]-CC-49-IgG and [¹⁷⁷Lu(BFC)]-CC-49-IgG. The [¹⁵³Sm(BFC)]-CC-49-IgG or [¹⁷⁷Lu(BFC)]-CC-49-IgG was allowed to stand in a 0.2M NaOAc buffer at pH 6.0, 4.0 and 2.8, at room temperature, at a protein concentration of about 5 x 10⁻⁶M with about 0.5 complex /antibody. Samples were withdrawn at certain time intervals and analyzed by HPLC (GF-250 column) for the dissociation of ¹⁵³Sm or ¹⁷⁷Lu activity from the protein. In general, the study was carried out for five days or until 90% of the radioisotopes have become dissociated. Results are expressed as the initial rate of loss of the radioisotope per day. The results demonstrated the superior stability of ¹⁵³Sm(PA-DOTA), ¹⁷⁷Lu(PA-DOTA, ¹⁵³Sm(BA-DOTA), and ¹⁵³Sm(OMe-BA-DOTA) as compared with the standard [¹⁵³Sm(Bz-DTPA)] complex at acidic pH. Results are shown in the table below. This greater stability of the complexes also correlates well with the more rapid clearance of ¹⁵³Sm and ¹⁷⁷Lu from the body and non-target tissue (e.g. kidney, liver); see Figs. 1-14. BFC Isotope % Loss of Isotope/Day pH 6.0 4.0 2.8 Bz-DTPA ¹⁵³Sm <2 35 35 PA-DOTA ¹⁵³Sm <2 <2 <2 BA-DOTA ¹⁵³Sm <2 <2 <2 PA-DOTA ¹⁷⁷Lu <2 <2 <2 MeOBA-DOTA ¹⁵³Sm <2 <2 <2 EA-DO3A ¹⁵³Sm <2 90 95 Example XXI (A and B) In vivo localization of α-(2-methoxy-5-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, samarium-153 complex labeled IgG and F(ab')₂; [¹⁵³Sm(MeO-BA-DOTA)]-IgG and [¹⁵³Sm(MeO-BA-DOTA)]-F(ab')₂. The titled compounds were prepared according to the procedures described in Examples V, VI, and XII, and the in vivo studies were conducted by the procedures of Example XI. Results are shown in Tables VIA and VIB. Example XXII Preparation of ¹⁵³Sm(PA-DOTMA) complex. To 100 microliters (µl) of ¹⁵³Sm (0.3 x 10⁻³M in 0.01N HCl; 5 mCi) were added 6 µl of PA-DOTMA (high R f diastereomer prepared by the procedure of Example 29); 5 mM in Milli-Q™ water), 20 µl of a MES buffer (1.0M, pH 6) and 1 µl of a HEPES buffer (0.5M, pH 8.7). This solution was mixed on a vortex mixer and the final pH of the mixture was about 6. After heating the mixture at 90°C for 30 min, it was anlyzed by HPLC on GF-250 column for chelation efficiency, and yields of 90 percent or better, were generally obtained. Characterization of the ¹⁵³Sm-PA-DOTMA complex was provided by comparison with the non-radioactive-Sm complex, which had been synthesized and characterized independently in Example 42. Example XXIII Preparation of ¹⁵³Sm(SCN-PA-DOTMA). To the ¹⁵³SmPA-DOTMA complex prepared in Example XXII and having been cooled for 20 min. at room temperature was added 10 µl of a 1 percent thiophosgene solution in 90 percent acetonitrile-water medium. The mixture was mixed vigorously on a vortex mixer, and allowed to stand at room temperature for between 5 to 20 min. The reaction took place instaneously as monitored by HPLC anaylsis. To purified the activated ¹⁵³Sm complex, it was extracted 3 times (200 µl each) with chloroform and the aqueous layer was passed throught as PRP cartridge (PRP cartridge = Mini-clean™ cartridge from Alltech Associates, Deerfield, IL) pretreated with 5 ml of methanol and 5 ml of a MES buffer (20 mM, pH 5.8). After being washed with 5 ml of the MES buffer and 5 ml of Milli-Q™ water, it was extracted with 900 µl of 90 percent acetontrile to recover approximately 90 percent of the ¹⁵³Sm activity, with the first 100 µl discarded. The mixture was evaporated to dryness under reduced pressure at temperatures below 40°C, and the residue which contained mostly the title product was used for conjugation to the antibody. Example XXIV Conjugation of ¹⁵³Sm(SCN-PA-DOTMA) to IgG and F(ab′)2 CC₄₉. In general, the antibody was concentrated and exchanged into a carbonate buffer (pH 9.1 or 9.5, 50 mM) in a Centricon™ concentrator (30 K molecular weight cut off) to result in a protein concentration of 1.5 x 10⁻⁴M or greater. To conjugate, a small volume of the carbonate buffer, that which is required to bring the final protein concentration to 1.5 x 10⁻⁴M, is added to the isothiocyanato derivative of ¹⁵³Sm(PA-DOTMA) (prepared in Example XXIII), followed by the concentrated antibody, of equimolar to the BFC-¹⁵³Sm complex. The mixture was mixed on a vortex mixer and allowed to react at room temperature for 1 hour or until 40 to 50 percent of ¹⁵³Sm become bound to the antibody, as shown by HPLC analysis on a GF-250 column. The labeled antibody was isolated by two consecutive centrifugal gel filtrations on Sephadex™ G-25 columns (2.2 ml). The homgeneity, integrity and immunoreactivity of the labeled antibody was analyzed by HPLC analysis and standard biochemical techniques described previously. Example XXV Biodistribution Studies of ¹⁵³Sm(PA-DOTMA) labeled IgG and F(ab′)2 CC₄₉. The studies were conducted in the similar fashion as described in Example XI. Results are shown in Tables VIIA and VIIB. See Figures 15-28. Example XXVI Preparation of ¹⁷⁷Lu (PA-DOTMA) Complex. To 30 µl of ¹⁷⁷Lu ( 6 x 10⁻³M in 1.1N HCl; 4 mCi) was added 36 µl of PA-DOTMA (prepared by the procedure of Example 29); 5 mM solution in milli-Q™ water). The solution was mixed on a vortex mixer, and 115 µl of a MES buffer (1.0M, pH 6.0) was added to neutralize the solution to about pH 5.5 to 6. This was heated at 90°C for 30 minutes to result in better than 90% chelation. The mixture was passed through a PRP cartridge pretreated with 5 ml of methanol and 5 ml of a MES buffer (20 mM, pH 5.8). It was washed with 5 ml of Milli-Q™ waste. The complex extracted in 1000 µl of 90% acetonitrile accounted for 78% of the starting ¹⁷⁷Lu activity (discarding the first 100 µl of the extract). Example XXVII Preparation of ¹⁷⁷Lu(SCN-PA-DOTMA). To the ¹⁷⁷Lu(PA-DOTMA) complex in 90% acetonitrile obtained in Example XXVI was added 6 µl of a 10% thiophosgen in 90% acetonitrile. This solution was mixed on a vortex mixer, and after 20 minutes, analyzed for the formation of the isothiocyanate derivative by HPLC. The reaction is, in general, quantitative. Removal of the solvent and the excess thiophosgene was accomplished by evaporation under reduced pressure at temperatures below 40°C for 1 to 2 hours. The residue was used for conjugation with the antibody. Example XXVIII Conjugation of ¹⁷⁷Lu(PA-DOTMA) to IgG CC49. The antibody IgG CC49 in a carbonate buffer (50 mM, pH 9.1) was mixed with an equimolar quantity of the isothiocyanato derivative (prepared by the procedure of from Example XXVII) in the same buffer. The reaction was continued for 70 min at an antibody concentration of 1.5 x 10⁻⁴M, and the labeled antibody was isolated and characterized according to procedures described in Example XXIV. Example XXIX Long Term Biodistribution Studies of ¹⁷⁷Lu(PA-DOTMA) Labeled IgG CC49. The long term animal test was conducted with the ¹⁷⁷Lu labeled antibody, taking advantage of its long half-life time (161 hours). It was carried out in Balb/c mice over a three week period, according to protocols described in Example XI. Results are shown in Table VIIIA. See Figures 29-34. In the Figures, which plot the data from the following tables, the symbols used were: Conjugates Symbol Table Figures Bio. Example [¹⁵³Sm(EA-DO3A)]-IgG-CC-49 ▵ IA 1-7 IX [¹⁵³Sm(EA-DO3A)]-F(ab′2)-CC-49 ▵ IB 8-14 X [¹⁵³Sm(Bz-DTPA)]-IgG-CC-49 ○ IC 1-7 ZA [¹⁵³Sm(Bz-DTPA)]-F(ab′2)-CC-49 ○ ID 8-14 ZA [¹⁵³Sm(PA-DOTA)]-IgG-CC-49 □ IIA 1-7 XII [¹⁵³Sm(PA-DOTA)]-F(ab′2)-CC-49 □ IIB 8-14 XIII [¹⁵³Sm(BA-DOTA)]-IgG-CC-49 ▪ IIIA 1-7 XV [¹⁵³Sm(BA-DOTA)]-F(ab′2)-CC-49 ▪ IIIB 8-14 XVI [¹⁵³Sm(PA-DOTMA)]-IgG-CC-49 ▿ VIIA 15-21 XXIV [¹⁵³Sm(PA-DOTMA)]-F(ab′2)-CC-49 ▿ VIIB 22-28 XXV [¹⁷⁷Lu(PA-DOTMA)]-IgG-CC-49  VIIIA 29-34 XXIX In the accompanying Figures the data represents the following:

Claims: Claims for the following Contracting States : AT, BE, CH, DE, FR, GB IT, LI, LU, NL, SE A compound of the formula: wherein: each Q is independently hydrogen or (CHR⁵ ) p CO₂R; Q¹ is hydrogen or (CHR⁵ ) w CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least two of the sum of Q and Q¹ must be other than hydrogen, and that when Q¹ is hydrogen, R³ must be other than hydrogen; each R⁵ independently is hydrogen or C₁-C₄ alkyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p = 1 or 2; r = 0 or 1; w = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond, and the sum of r and w is 0 or 1; R² is hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido or carboxyl; R³ is C₁-C₄ alkoxy, -OCH₂CO₂H, hydroxy or hydrogen; R⁴ is hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; with the proviso that R² and R⁴ cannot both be hydrogen but one of R² and R⁴ must be hydrogen; or a pharmaceutically acceptable salt thereof. A compound of Claim 1 wherein the pharmaceutically acceptable salt is selected from the group consisting of potassium, sodium, lithium, ammonium, calcium, magnesium, and hydrogen chloride adducts. A compound of Claim 1 wherein R and R⁵ are both hydrogen. A compound of Claim 1 wherein R is hydrogen, R⁵ is methyl and w is 0. A compound of Claim 1 wherein n and r are both 0 and m is 0 through 5. A compound of Claim 1 wherein R³ and R⁴ are hydrogen. A compound of Claim 1 having the formula wherein: each Q is independently hydrogen or CHR⁵CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at lease two of Q must be other than hydrogen; m is an integer from 0 to 5 inclusive; R², R³, R⁴ and R⁵ are defined as in claim 1; or a pharmaceutically acceptable salt thereof. A compound of Claim 7 having the formula wherein: Q and m are defined as in claim 7; R² is selected from the group consisting of nitro, amino, isothiocyanato, and semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; or a pharmaceutically acceptable salt thereof. The compound of Claim 7 which is 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester. The compound of Claim 8 which is 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, hydrochloride salt. The compound of Claim 8 which is 1-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid. The compound of Claim 8 which is 1-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, hydrochloride salt. A compound of Claim 7 having the formula wherein: Q and m are defined as in claim 7; R³ is selected from the group consisting of C₁-C₄ alkoxy, -OCH₂CO₂H and hydroxy; R⁴ is selected from the group consisting of nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; or a pharmaceutically acceptable salt thereof. The compound of Claim 13 which is 1-(2-methoxy-5-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid. The compound of Claim 13 which is 1-(2-hydroxy-5-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid. A compound of Claim 1 having the formula wherein: each Q is independently hydrogen or CHR⁵CO₂R; Q¹ is hydrogen or (CHR⁵) w CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least two of the sum of Q and Q¹ must be other than hydrogen and one of Q is hydrogen; m is an integer from 0 to 5 inclusive; w is 0 or 1; R², R³, R⁴ and R⁵ are defined as in claim 1; or a pharmaceutically acceptable salt thereof. The compound of Claim 16 wherein R is hydrogen and R⁵ is C₁₋₄ alkyl. A compound of Claim 16 having the formula wherein: each Q is independently hydrogen or CHR⁵CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least one Q must be other than hydrogen; m is an integer from 0 to 5 inclusive; R², R³, R⁴ and R⁵ are defined as in claim 1; or a pharmaceutically acceptable salt thereof. A compound of Claim 18 having the formula wherein: Q and m are defined as in claim 18; R² is selected from the group consisting of nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; or a pharmaceutically acceptable salt thereof. The compound of Claim 19 which is α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic 4,7,10-tris-(R-methylacetic) acid, 1-isopropyl-4,7,10-trimethyl ester. The compound of Claim 19 which is α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic 4,7,10-tris-(R-methylacetic) acid. The compound of Claim 19 which is α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris-(R-methylacetic) acid. The compound of Claim 19 which is α-[2-(4-aminophenyl)ethyl]-1 4,7,10-tetraazacyclododecane-1,4,10-triacetic acid, mixed ammonium, potassium salt. The compound of Claim 19 which is α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid. The compound of Claim 19 which is α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,10-triacetic acid. The compound of Claim 19 which is α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. The compound of Claim 19 which is α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. The compound of Claim 19 which is α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester. The compound of Claim 19 which is α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester. The compound of Claim 19 which is α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. The compound of Claim 19 which is α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. A compound of Claim 18 having the formula wherein: each Q is independently hydrogen or CHR⁵CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least one Q must be other than hydrogen; m is an integer from 0 to 5 inclusive; R³ and R⁵ are defined as in claim 1; R⁴ is selected from the group consisting of nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; or a pharmaceutically acceptable salt thereof. The compound of Claim 32 which is α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. The compound of Claim 32 which is α-(2-methoxy-5-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, tetraamonium salt. The compound of Claim 32 which is α-(2-methoxy-5-isothiocynatophenyl)-1,4,7,10-tetraazacyolododecane-1,4,7,10-tetraacetic acid, tetraamonium salt. A complex comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof; complexed with an ion of a metal selected from La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y and Sc. A complex of Claim 36 wherein the metal is Sm, Lu or Y. A complex of Claim 36 wherein the metal is ¹⁵³Sm, ¹⁶⁶Ho, ⁹⁰Y, ¹⁴⁹Pm, ¹⁵⁹Gd, ¹⁴⁰La, ¹⁷⁷Lu, ¹⁷⁵Yb, ⁴⁷Sc, or ¹⁴²Pr. A complex of Claim 38 wherein the metal is ¹⁵³Sm, ¹⁷⁷Lu or ⁹⁰Y. A complex of any one of Claims 36 through 39 wherein the metal ion is complexed with the compound of Claims 7, 8, 13, 16, 18, 19 or 32. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 26. A complex of Claim 41 wherein the metal is ¹⁵³Sm or ⁹⁰Y. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 27. A complex of Claim 43 wherein the metal is ¹⁵³Sm. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 30 or 31. A complex of Claim 45 wherein the metal is ¹⁵³Sm, ⁹⁰Y or ¹⁷⁷Lu. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 32. A complex of Claim 47 wherein the metal is ¹⁵³Sm ⁹⁰Y or ¹⁷⁷Lu. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 10. A complex of Claim 49 wherein the metal is ¹⁵³Sm. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 11. A complex of Claim 51 wherein the metal is ¹⁵³Sm. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 34. A complex of Claim 53 wherein the metal is ¹⁵³Sm. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 35. A complex of Claim 55 wherein the metal is ¹⁵³Sm. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 21. A complex of Claim 57 wherein the metal is ¹⁵³Sm, ⁹⁰Y or ¹⁷⁷Lu. A complex of Claim 38 wherein the metal ion is complexed with the compound of Claim 22. A complex of Claim 73 wherein the metal is ¹⁵³Sm ⁹⁰Y or ¹⁷⁷Lu. A conjugate comprising a complex according to claim 36 with the proviso that R² and R⁴ cannot be nitro, and covalently attached to an antibody or antibody fragment. The conjugate of Claim 61 wherein the metal is ¹⁵³Sm, ¹⁶⁶Ho, ⁹⁰Y, ¹⁴⁹Pm, ¹⁵⁹Gd, ¹⁴⁰La, ¹⁷⁷Lu, ¹⁷⁵Yb, ⁴⁷Sc or ¹⁴²Pr. The conjugate of Claim 62 wherein the metal is ¹⁵³Sm, ⁹⁰Y or ¹⁷⁷Lu. A conjugate of any one of Claims 61 through 63 wherein the antibody or antibody fragment is a monoclonal antibody or fragment thereof. A conjugate of Claim 64 wherein the antibody or antibody fragment is CC-49 (ATCC HB 9459), CC-49 F(ab')₂, CC-83 (ATCC HB 9453), CC-83 F(ab')₂ or B72.3 (ATCC HB 8108). A conjugate of any one of Claims 61 through 63 wherein the compound is as defined in Claims 7, 8, 13, 16, 18, 19 or 32. A conjugate of any one of Claims 62 through 65 wherein the metal ion is ¹⁵³Sm complexed with the compound of Claim 27. A conjugate of any one of Claims 62 through 65 wherein the metal ion is ¹⁵³Sm, ⁹⁰Y or ¹⁷⁷Lu complexed with the compound of Claim 32. A conjugate of any one of Claims 62 through 65 wherein the metal ion is ¹⁵³Sm complexed with the compound of Claim 35. A conjugate of any one of Claims 62 through 65 wherein the metal ion is ¹⁵³Sm, ⁹⁰Y or ¹⁷⁷Lu complexed with the compound of Claim 22. A conjugate comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof; covalently attached to an antibody or antibody fragment. A conjugate of Claim 71 wherein the antibody or antibody fragment is a monoclonal antibody or fragment thereof. A conjugate of Claim 72 wherein the antibody or antibody fragment is CC-49 (ATCC HB 9459), CC-49 F(ab')₂, CC-83 (ATCC HB 9453), CC-83 F(ab')₂ or B72.3 (ATCC HB 8108). A conjugate of any one of Claims 71 through 73 wherein the compound is as defined in Claims 7, 8, 13, 16, 18, 19 or 32. A pharmaceutical formulation comprising a conjugate as claimed in any one of Claims 61 through 70 with a pharmaceutically acceptable carrier. A process for preparing a compound of the formula wherein: each Q is independently hydrogen or (CHR⁵) p CO₂R; Q¹ is hydrogen or (CHR⁵) w CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least two of the sum of Q and Q¹ must be other than hydrogen, and that when Q¹ is hydrogen, R³ must be other than hydrogen; each R⁵ independently is hydrogen or C₁-C₄ alkyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p = 1 or 2; r = 0 or 1; w = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond, and the sum of r and w is 0 or 1; R² is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; R³ is selected from the group consisting of C₁-C₄ alkoxy, -OCH₂CO₂H, hydroxy and hydrogen; R⁴ is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; with the proviso that R² and R⁴ cannot both be hydrogen but one of R² and R⁴ must be hydrogen; or a pharmaceutically acceptable salt thereof; which comprises any one of the following steps: (A) reacting a compound of the formula wherein: X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; r = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond; with an α-halocarboxylic acid ester of the formula BrCH₂CO₂R where each R independently is benzyl or C₁-C₄ alkyl; in the presence of an organic solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹, R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is nitro; or (B) reacting the product of step (A) with hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹, R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is amino; or (C) reacting a compound of the formula (IIIA) as defined above with a hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions, followed by hydrogen chloride gas in the presence of a solvent to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹, R³, R⁴ are hydrogen; and R² is amino; or (D) reacting the product of step (C) with an α-halocarboxylic acid ester of the formula BrCH₂CO₂R where each R independently is benzyl or C₁-C₄ alkyl; in the presence of an organic solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹, R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is amino; or (E) reacting a compound of the formula wherein: Q¹ is (CHR⁵) w CO₂R; each R independently is benzyl or C₁-C₄ alkyl; each R⁵ independently is hydrogen or C₁-C₄ alkyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; r = 0 or 1; w = 0 or 1; with the proviso that the sum of r and w is 0 or 1; with an α-halocarboxylic acid ester of the formula BrCH₂CO₂R where each R independently is benzyl or C₁-C₄ alkyl; in the presence of an organic-solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, Q¹, m, n, r are defined as before; R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is nitro; or (F) reacting the product of step (E) with hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions, to provide the compounds of formula (IA) wherein: X, Y, Q¹, m, n, r are defined as before; R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is amino; or (G) reacting the product of either step (B) or (D) with a desterifing agent, such as a strong acid, to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹, R³, R⁴, R⁵ are hydrogen; R is hydrogen; and R² is amino; or (H) reacting the product of step (F) with a desterifing agent, such as a strong acid, to provide the compounds of formula (IA) wherein: X, Y, Q¹, m, n, r are defined as before; R³, R⁴, R⁵ are hydrogen; R is hydrogen; and R² is amino; or (I) reacting a compound of formula (VA) as defined above with an optically active α-benzene sulfonate of the formula wherein R and R⁵ are defined as before, to provide the compounds of formula (IA) wherein: X, Y, Q¹, R⁵ m, n, r are defined as before; R³ and R⁴ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is nitro; or (J) reacting the product of step (I) with hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions, to provide the compounds of formula (IA) wherein: X, Y, Q¹ , R⁵, m, n, r are defined as before; R³ and R⁴ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is amino; or (K) reacting the product of step, (J) with a desterifing agent, such as a strong acid, to provide the compounds of formula (IA) wherein. X, Y, Q¹ , R⁵, m, n, r are defined as before; R³, R⁴ and R are hydrogen; and R² is amino; or (L) reacting a compound of the formula wherein: X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; R³' is C₁-C₄ alkoxy, -OCH2CO2H or hydroxy; n is 0 or 1; m is an integer from 0 to 10 inclusive; r = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond; with an α-halocarboxylic acid of the formula BrCH₂CO₂H in the presence of an organic solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, R³', m, n, r are defined as before; Q¹ and R² are hydrogen; and R⁴ is nitro; or (M) reacting the product of step (L) with hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions to provide the compounds of formula (IA) wherein: X, Y, R³', m, n, r are defined as before; Q¹,R, R² and R⁵ are hydrogen; and R² is amino; or (N) reacting a compound of the formula wherein: X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; Q¹ is CH₂CO₂R; R is benzyl or C₁₋₄ alkyl; n is 0 or 1; m is an integer from 0 to 10 inclusive; r = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond; with an α-halocarboxylic acid of the formula BrCH₂CO₂R where R is defined as before; in the presence of an organic solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, Q¹, Q, m, n, r are defined as before; R² is hydrogen; and R⁴ is nitro; or (O) reacting the product of step (N) with a desterifing agent, such as a strong acid, followed by a hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions to provide the compounds of formula (IA) wherein: X, Y, Q¹, Q, m, n, r are defined as before; R, R² and R⁵ are hydrogen; and R² is amino; or (P) reacting the product of step (G), (F), (K), (M) or (O) with thiophosgene to provide the corresponding compound wherein R² or R⁴ is isothiocyanato. A process for preparing a mono-N-alkylated polyazamacrocycle which comprises reacting an α-halocarboxylic-acid-ester with between one to five equivalents of a 1,4,7,10-tetraazacyclododecane in a solvent which will not promote a proton transfer. The process of claim 77 wherein the α-halocarboxylic-acid-ester is d,l-2-bromo-4(4-nitrophenyl)butanoic acid methylester, 2-bromo-2-(4-nitrophenyl)ethanoic acid-methylester,α-bromo-(2-methoxy-5-nitrophenyl)acetic-acid-methylester, or d,l-2-bromo-4-(4-nitrophenyl)-butanoic acid isopropylester. Claims for the following Contracting States : ES, GR A process for preparing a compound of the formula wherein: each Q is independently hydrogen or (CHR⁵) p CO₂R; Q¹ is hydrogen or (CHR⁵) w CO₂R; each R independently is hydrogen, benzyl or C₁-C₄ alkyl; with the proviso that at least two of the sum of Q and Q¹ must be other than hydrogen, and that when Q¹ is hydrogen, R³ must be other than hydrogen; each R⁵ independently is hydrogen or C₁-C₄ alkyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p = 1 or 2; r = 0 or 1; w = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond, and the sum of r and w is 0 or 1; R² is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; R³ is selected from the group consisting of C₁-C₄ alkoxy, -OCH₂CO₂H, hydroxy and hydrogen; R⁴ is selected from the group consisting of hydrogen, nitro, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido and carboxyl; with the proviso that R² and R⁴ cannot both be hydrogen but one of R² and R⁴ must be hydrogen; or a pharmaceutically acceptable salt thereof; which comprises any one of the following steps: (A) reacting a compound of the formula wherein: X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; r = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond; with an α-halocarboxylic acid ester of the formula BrCH₂CO₂R where each R independently is benzyl or C₁-C₄ alkyl; in the presence of an organic solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹, R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is nitro; or (B) reacting the product of step (A) with hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹, R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is amino; or (C) reacting a compound of the formula (IIIA) as defined above with a hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions, followed by hydrogen chloride gas in the presence of a solvent to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹, R³, R⁴ are hydrogen; and R² is amino; or (D) reacting the product of step (C) with an α-halocarboxylic acid ester of the formula BrCH₂CO₂R where each R independently is benzyl or C₁-C₄ alkyl; in the presence of an organic solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹, R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is amino; or (E) reacting a compound of the formula wherein: Q¹ is (CHR⁵) w CO₂R; each R independently is benzyl or C₁-C₄ alkyl; each R⁵ independently is hydrogen or C₁-C₄ alkyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; r = 0 or 1; w = 0 or 1; with the proviso that the sum of r and w is 0 or 1; with an α-halocarboxylic acid ester of the formula BrCH₂CO₂R where each R independently is benzyl or C₁-C₄ alkyl; in the presence of an organic solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, Q¹, m, n, r are defined as before; R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is nitro; or (F) reacting the product of step (E) with hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions, to provide the compounds of formula (IA) wherein: X, Y, Q¹, m, n, r are defined as before; R³, R⁴, R⁵ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is amino; or (G) reacting the product of either step (B) or (D) with a desterifing agent, such as a strong acid, to provide the compounds of formula (IA) wherein: X, Y, m, n, r are defined as before; Q¹ R³, R⁴, R⁵ are hydrogen; R is hydrogen; and R² is amino; or (H) reacting the product of step (F) with a desterifing agent, such as a strong acid, to provide the compounds of formula (IA) wherein: X, Y, Q¹ , m, n, r are defined as before; R³, R⁴, R⁵ are hydrogen; R is hydrogen; and R² is amino; or (I) reacting a compound of formula (VA) as defined above with an optically active α-benzene sulfonate of the formula wherein R and R⁵ are defined as before, to provide the compounds of formula (IA) wherein: X, Y, Q¹, R⁵ m, n, r are defined as before; R³ and R⁴ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is nitro; or (J) reacting the product of step (I) with hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions, to provide the compounds of formula (IA) wherein: X, Y, Q¹, R⁵, m, n, r are defined as before; R³ and R⁴ are hydrogen; R is C₁₋₄ alkyl or benzyl; and R² is amino; or (K) reacting the product of step (J) with a desterifing agent, such as a strong acid, to provide the compounds of formula (IA) wherein: X, Y, Q¹, R⁵, m, n, r are defined as before; R³, R⁴ and R are hydrogen; and R² is amino; or (L) reacting a compound of the formula wherein: X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; R³' is C₁-C₄ alkoxy, -OCH2CO2H or hydroxy; n is 0 or 1; m is an integer from 0 to 10 inclusive; r = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond; with an α-halocarboxylic acid of the formula BrCH₂CO₂H in the presence of an organic solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, R³', m, n, r are defined as before; Q¹ and R² are hydrogen; and R⁴ is nitro; or (M) reacting the product of step (L) with hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions to provide the compounds of formula (IA) wherein: X, Y, R³', m, n, r are defined as before; Q¹,R, R² and R⁵ are hydrogen; and R² is amino; or (N) reacting a compound of the formula wherein: X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; Q¹ is CH₂CO₂R; R is benzyl or C₁₋₄ alkyl; n is 0 or 1; m is an integer from 0 to 10 inclusive; r = 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond; with an α-halocarboxylic acid of the formula BrCH₂CO₂R where R is defined as before; in the presence of an organic solvent and base, at a temperature of from 0°C to reflux, to provide the compounds of formula (IA) wherein: X, Y, Q¹, Q, m, n, r are defined as before; R² is hydrogen; and R⁴ is nitro; or (O) reacting the product of step (N) with a desterifing agent, such as a strong acid, followed by a hydrogenation agent, such as Pd/C with hydrogen, under standard reaction conditions to provide the compounds of formula (IA) wherein: X, Y, Q¹, Q, m, n, r are defined, as before; R, R² and R⁵ are hydrogen; and R² is amino; or (P) reacting the product of step (G), (F), (K), (M) or (O) with thiophosgene to provide the corresponding compound wherein R² or R⁴ is isothiocyanato. A process of Claim 1 for preparing a pharmaceutically acceptable salt of the compound of formula (IA) which comprises reacting the compound of formula (IA) with a reagent, by known methods, to obtain potassium, sodium, lithium, ammonium, calcium, magnesium, or hydrogen chloride adducts as the pharmaceutically acceptable salt. The process of Claim 1(B) for preparing 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester which comprises reacting 1-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester with hydrogen and palladium on carbon. The process of Claim 1(G) for preparing 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, hydrochloride salt which comprises reacting 1-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, 4,7,10-trimethyl ester with hydrochloric acid. The process of Claim 1(P) for preparing 1-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyolo dodecane-4,7,10-triacetic acid which comprises reacting 1-[2-(4-Aminophenyl)ethyl]-1,4,7,10-tetraazacyclo-dodecane-4,7,10-triacetic acid, hydrochloride salt with thiophosgene. The process of Claim 1(A) for preparing 1-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid, hydrochloride salt which comprises reacting 1-(4-aminobenzyl)-1,4,7-10-tetraaacyclododecane, tetrahydrochloride salt with methylbromoacetate. The process of Claim 1(M) for preparing 1-(2-methoxy-5-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid which comprises reacting 1-(2-methoxy-5-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid with hydrogen in a Parr bomb. The process of Claim 1(M) for preparing 1-(2-hydroxy-5-aminobenzyl)-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid which comprises reacting N-(2-hydroxy-5-nitrobenzyl )-1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid with hydrogen and PtO₂. The process of Claim 1(J) for preparing α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic 4,7,10-tris-(R-methylacetic) acid, 1-isopropyl-4,7,10-trimethyl ester which comprises reacting α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclo-dodecane-1-(R,S)-acetic-4,7,10-tris-(R-methylacetic) acid, 1-isopropyl-4,7,10-trimethyl ester with hydrogen and palladium on carbon. The process of Claim 1(K) for preparing α-[2-(4-aminophenyl)ethyl]1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic 4,7,10-tris-(R-methylacetic) acid which comprises reacting α-▪2-(4-aminophenyl)ethyl▪-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris-(R- methylacetic) acid, 1-isopropyl-4,7,10-trimethyl ester with hydrochloric acid. The process of Claim 1(P) for preparing α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic-4,7,10-tris-(R-methylacetic) acid which comprises reacting α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-(R,S)-acetic 4,7,10-tris-(R-methylacetic) acid with thiophosgene. The process of Claim 1(F) for preparing α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid which comprises reacting α-(4-nitrophenyl-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid with hydrogen and PtO₂. The process of Claim 1(F) for preparing α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,10-triacetic acid which comprises reacting α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,10-triacetic acid with hydrogen and PtO₂. The process of Claim 1(F) for preparing α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid which comprises reacting α-(4-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with hydrogen and PtO₂. The process of Claim 1(P) for preparing α-(4-isothiocyanatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid which comprises reacting α-(4-aminophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with thiophosgene. The process of Claim 1(E) for preparing α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester which comprises reacting α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1-acetic acid, 1-methyl ester with methyl bromoacetate. The process of Claim 1(F) for preparing α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester which comprises reacting α-[2-(4-nitrophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester with hydrogen and palladium-on-carbon. The process of Claim 1(H) for preparing α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid which comprises reacting α-[2-(4-aminophenyl)-ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7,10-tetramethyl ester with hydrodrochloric acid. The process of Claim 1(P) for preparing α-[2-(4-isothiocyanatophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid which comprises reacting α-[2-(4-aminophenyl)ethyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with thiophosgene. The process of Claim 1(O) for preparing α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid which comprises reacting α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, tetramethyl ester with hydrochloric acid. The process of Claim 1(O) for preparing α-(2-methoxy-5-aminophenyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid, tetraamonium salt which comprises reacting α-(2-methoxy-5-nitrophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with hydrogen and PtO₂. The process of Claim 1(P) for preparing α-(2-methoxy-5-isothiocynatophenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, tetraamonium salt which comprises reacting α-(2-methoxy-5-aminophenyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid with thiophosgene. A process for preparing a complex of a compound as claimed in any one of Claims 1 through 22 with an ion of a metal selected from La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y and Sc which comprises reacting the compound with the metal ion. The process of Claim 23 wherein the metal is ¹⁵³Sm, ¹⁶⁶Ho, ⁹⁰Y, ¹⁴⁹Pm, ¹⁵⁹Gd, ¹⁴⁰La, ¹⁷⁷Lu, ¹⁷⁵Yb, ⁴⁷Sc, or ¹⁴²Pr. The process of Claim 24 wherein the metal is ¹⁵³Sm, ¹⁷⁷Lu or ⁹⁰Y. A process of any one of Claims 23 through 25 wherein the reaction is heated. A process for preparing a conjugate containing a complex of a compound as claimed in any one of Claims 1 through 22 complexed with an ion of a metal selected from La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y and Sc, which comprises covalently attaching the complex to an antibody or antibody fragment. The process of Claim 27 wherein the metal is ¹⁵³Sm, ¹⁶⁶Ho, ⁹⁰Y, ¹⁴⁹Pm, ¹⁵⁹Gd, ¹⁴⁰La, ¹⁷⁷Lu, ¹⁷⁵Yb, ⁴⁷Sc, or ¹⁴²Pr. The process of Claim 28 wherein the metal is ¹⁵³Sm, ¹⁷⁷Lu or ⁹⁰Y. A conjugate of any one of Claims 27 through 29 wherein the antibody or antibody fragment is a monoclonal antibody or fragment thereof. A conjugate of Claim 30 wherein the antibody or antibody fragment is CC-49 (ATCC HB 9459), CC-49 F(ab')₂, CC-83 (ATCC HB 9453), CC-83 F(ab')₂ or B72.3 (ATCC HB 8108). A process for preparing a conjugate containing a compound as claimed in any one of Claims 1 through 22 covalently attached to an antibody or antibody fragment which comprises reacting the compound with an antibody or antibody fragment. A conjugate of Claim 32 wherein the antibody or antibody fragment is a monoclonal antibody or fragment thereof. A conjugate of Claim 33 wherein the antibody or antibody fragment is CC-49 (ATCC HB 9459), CC-49 F(ab')₂, CC-83 (ATCC HB 9453), CC-83 F(ab')₂ or B72.3 (ATCC HB 8108). A process for preparing a mono-N-alkylated polyazamacrocycle which comprises reacting an α-halocarboxylic-acid-ester with between one to five equivalents of a 1,4,7,10-tetraazacyclododecane in a solvent which will not promote a proton transfer. The process of claim 35 wherein the α-halocarboxylic-acid-ester is d,l-2-bromo-4(4-nitrophenyl)butanoic acid methylester, 2-bromo-2-(4-nitrophenyl)ethanoic acid-methylester,α-bromo-(2-methoxy-5-nitrophenyl)acetic-acid-methylester, or d,l-2-bromo-4-(4-nitrophenyl)-butanoic acid isopropylester.

Inventors: BAUGHMAN SHARON, CHENG ROBERTA C, FORDYCE WILLIAM A, FRANK RICHARD KEITH, GARLICH JOSEPH R, GOECKELER WILLIAM F, KIEFER GARRY, KRUPER WILLIAM F JR, MCMILLAN KENNETH, SIMON JAIME J, WILSON DAVID A, BAUGHMAN, SHARON, CHENG, ROBERTA C., FORDYCE, WILLIAM A., FRANK, RICHARD KEITH, GARLICH, JOSEPH R., GOECKELER, WILLIAM F., KIEFER, GARRY, KRUPER, WILLIAM F., JR., MCMILLAN, KENNETH, SIMON, JAIME J., WILSON, DAVID A.
Applicants: DOW CHEMICAL CO, THE DOW CHEMICAL COMPANY
Application year: 1989
Main classification: C07D257
IPC codes: A61K9, C07K16, A61K51, A61K31, A61P35, C07D257, A61K39