bluuebunny/crossref_metadata_2025 huggingface dataset:
Labelling of human serum albumin with 99mTc using Sn(II) citrate
Authors: El‐Kolaly M. T. , El‐Wetery A. S.
Published: October 2006

Labelling of human serum albumin (HSA) with 99m Tc, at neutral pH, using Sn(II) citrate as reducing agent is described. At pH 7.4, more than 98% binding efficiency for 99m Tc‐HSA is achieved. 99mTc‐Sn‐citrate with high protein binding capacity is first formed as an intermediate complex and in the presence of albumin, a more stable 99mTc‐HSA complex is formed. 99mTc‐HSA complex is formed by ligand exchange and 30 min reaction time is sufficient for the complex formation of 99mTc‐HSA. Biodistribution in normal mice at 30 min obtained for 99mTc‐HSA prepared by Sn(II) citrate showed 30.3% injected dose in blood compared to 32.9–34.5% for 99mTc‐HSA prepared by Sn(II)Cl2. The presence of citrate stabilizes Sn(II) ions towards oxidation and hydrolysis. The addition of ascorbic acid did not increase the percent yield of 99mTc‐HSA and has adverse effect on its biological distribution.
The synthesis of (2R)‐ and (2S)‐[2‐3H]‐propionic acid
Authors: Parry Ronald J. , Turakhia Rajesh
Published: October 2006

A practical synthesis of (2R)‐ and (2S)‐[2‐3H]‐propionic acid is described. The key steps in the synthesis are the reduction of [formyl‐3H]‐3‐methoxy‐4‐mesyloxybenzaldehyde with R‐ or S‐Alpine Borane to (7S)‐ and (7R)‐[7‐3H]‐3‐methoxy‐4‐mesyloxybenzyl alcohol and the use of the vanillyl moiety as a masked carboxyl group.
Syntheses of deuterated leu‐enkephalins and their use as internal standards for the quantification of leu‐enkephalin by fast atom bombardment mass spectrometry
Authors: Benfenati E. , Icardi G. , Chen S. , Fanelli R.
Published: October 2006

We have developed a synthetic method for the preparation of di‐ and pentadeuterated leu‐enkephalin (LE), Tyr‐Gly‐Gly‐Phe‐Leu, by proton‐deuterium exchange using CF3COO2H. Four to six deuterium atoms are introduced using a reaction temperature of 120°C and if 5% of 2H2O is added the di‐deuterated LE is obtained. These deuterated compounds are used as internal standards to plot calibration curves of LE using fast atom bombardment mass spectrometry.
Synthesis of [11C]‐sarin
Authors: Prenant C. , Crouzel C.
Published: October 2006

[11C]‐acetone, prepared from 11CO2 and methyllithium, was reduced to [11C]‐isopropanol. The latter reacted with methylphosphonic acid difluoride in the presence of diisopropylamine, to yield [11C]‐sarin.

3.4 GBq (100 mCi) of [11C]‐sarin may be obtained from about 55.5 GBq (1.5 Ci) of 11CO2 in 40 minutes. The product purified by HPLC, is obtained with a specific radioactivity ranging from 22.2 to 33.3 GBq (600 to 900 mCi/μmol.).
Development of techniques for the synthesis of radiolabelled trimethyloxonium tetrafluoroborate
Authors: Mahnir Vladimir M. , Zaharov Sergey S.
Published: October 2006

The design of a vacuum manifold for the synthesis of radiolabelled trimethyloxonium tetrafluoroborate from radiolabelled methyl iodide and triethyloxonium tetrafluoroborate is described.
Enantiospecific synthesis of [1‐3H]‐(+)‐pseudoephedrine hydrochloride
Authors: Hill John A. , Scharver Jeffrey D.
Published: October 2006

The naturally occurring dextrorotary enantiomer (+)‐pseudoephedrine, 1, was synthesized (1) in the [3H]‐labelled form with specific activity 17.5 Ci/mmol suitable for development of a radioimmunoassay procedure. The chirally specific route from L‐alanine to [1‐3H]‐d‐pseudoephedrine hydrochloride was based on the use of α‐amino acids as chiral educts for asymmetric products as developed by Rapoport.
High yield preparation of pure 2‐radioiodo‐ketanserin of high specific activity, a serotonin S2 receptor tracer for spect
Authors: Mertens J. , Gysemans M. , Bossuyt‐Piron C. , Thomas M.
Published: October 2006

The synthesis of pure and high specific activity 2‐radioiodo‐Ketanserin is described. The Cu(1) assisted nucleophilic non‐isotopic exchange applied on 0.5 mg 2‐Br‐Ketanserin allows to obtain a labelling yield ≧ 90%. After appropriate semi‐preparative HPLC separation the tracer is further purified by means of a mini RP column technique, thus avoiding the inconveniences of evaporation of eluent. An overall radiochemical yield exceeding 75% of 2‐123I‐Ketanserin with a purity ≧ 99% ready for i.v. injection is obtained.
Synthesis of both 14C‐ and 3H‐ labelled trospectomycin and the assessment of their utility in biological studies
Authors: Constable D. A. , Dring L. G. , Jones J. R.
Published: October 2006

Three radiolabelled forms of trospectomycin (6′‐n‐propylspectinomycin sulphate hydrate) have been synthesised, namely [8′‐14C]‐, [6′,7′‐3H]‐, and [5′,6′,7′‐3H]‐trospectomycin. Although all three forms of the drug are metabolically stable and therefore suitable for use in animal studies the 14C compound is produced in poor yield as is the [6′,7′‐3H]trospectomycin. On the other hand, the [5′,6′,7′‐3H]‐form is produced in good yield and appears to be the labelled form of choice. Following subcutaneous administration of any of the labelled forms to rats, more than 50% of the dose was excreted in the urine as unchanged drug during the first 6h after dosing. Approximately 80% and 10% of the dose appeared in the urine and faeces respectively after 6 days.
Synthesis of tritium labelled 1‐(3,4‐dichlorophenyl)‐3‐(methylamino)propanol hydrochloride
Authors: Hill John A. , Wisowaty James C.
Published: October 2006

1‐(3,4‐Dichlorophenyl)‐3‐(methylamino)propanol hydrochloride, 1, a potential antidepressant, was synthesized by a two‐step method in the [3H]‐labelled form with specific activity 12.5 mCi/mmol suitable for drug metabolism and disposition studies (1).
Tritium labelling of highly selective probes for δ‐opioid receptors: [3H] Tyr‐D‐Ser(O‐t‐Bu)‐Gly‐Phe‐Leu‐Thr(DSTBULET) and [3H]Tyr‐D‐Ser(O‐t‐Bu)‐Gly‐Phe‐Leu‐Thr(O‐t‐Bu)(BUBU)
Authors: Fellion E. , Gacel G. , Roques B. P. , Roy J. , Morgat J. L.
Published: October 2006

The introduction of bulky residue (s) in linear enkephalin‐related hexapeptides represents a new approach in the design of selective probes for δ‐opioid receptors, displaying the appropriate criteria to investigate biological and pharmacological properties of the assumed binding site (δ) of endogenous enkephalins. The selectivities and high affinities of Tyr‐D‐Ser(O‐t‐Bu)‐Gly‐Phe‐Leu‐Thr(DSTBULET) and especially Tyr‐D‐Ser(O‐T‐Bu)‐Gly‐Phe‐Leu‐Thr(O‐t‐Bu) (BUBU) associated with a satisfactory resistance to peptidases, make them the most suitable δ–probes reported to date. In the present paper, we report the synthesis of DSTBULET and BUBU under tritiated forms with high specific radioactivities. These radio‐labelled probes will enable extensive in vitro and in vivo investigations of δ–opioid receptors properties to be carried out.
Synthesis of trideuteromethyl‐3(5) pyrazoles
Authors: Iranzo Gloria Y. , Elguero José
Published: October 2006

The synthesis of 3,5‐bis (trideuteromethyl) pyrazole was achieved by reaction of perdeuterated acetylacetone with perdeuterated hydrazine hydrate. Some unsuccessful attempts using alternative routes are also described.
Synthesis of deuterium labelled analogs of the ubiquinone headgroup
Authors: Dieks Henrik , Beyer Klaus
Published: October 2006

Deuterium labelled analogs of 2,3 ‐ dimethoxy ‐ 5 ‐ methyl ‐ 1,4 ‐ benzoquinone (2,3 ‐ dimethoxy ‐ 5 methyl[2H3] ‐ 1,4 ‐ benzoquinone; 2,3 ‐ dimethyoxy[2H6] ‐ 5 ‐ methyl ‐ 1,4 ‐ benzoquinone; 2,3 ‐ dimethoxy[2H6] ‐ 5 ‐ methyl[2H3] ‐ 1,4 ‐ benzoquinone) were prepared in five steps starting from 3,4,5 ‐ trihydroxybenzoic acid. The proposed synthetic route results in 100% specific labelling and gives good overall yields. Mass spectra of the labelled derivatives will be briefly discussed.
18F‐labelling of thiophene and N‐methylpyrrole
Authors: Crestoni Maria Elisa
Published: October 2006

2‐ and 3‐[18F]fluorothiophene and 2‐ and 3 [18F]fluoro‐N‐methyl pyrrole have been obtained by the reaction of thiophene and N‐methylpyrrole with molecular fluorine [18F]‐F2 under carefully controlled conditions.
Facile synthesis of D,L‐[34S]cysteine hydrochloride
Authors: Huynh‐Ba Tuong , Fay Laurent
Published: October 2006

The title compound was synthesized at the gram level in 66% yield by addition of [34S]thioacetic acid to α‐acetamidoacrylic acid, followed by acid hydrolysis.
A new method to prepare no‐carrier‐added iodinated spirodecanone derivatives:1 application to dopaminergic and serotoninergic ligands
Authors: Frangin Y. , Callet M. , Chalon S. , Huguet F. , Foulon C. , Desplanches G. , Baulieu J‐ L. , Besnard J‐C. , Guilloteau D.
Published: October 2006

Two new iodinated ligands for human brain exploration by SPECT were synthesized. For this purpose tosylethyl precursors were prepared in a one‐pot synthesis from ethylene glycol di‐p‐toluene sulfonate and potassium salt of spiperone, a D2 receptor antagonist, or spiroxatrine, a 5HT1A receptor antagonist. Substitution of the precursor tosyl group by iodide or radioiodide yielded respectively iodoethylspiperone, iodoethylspiroxatrine and their radioiodinated analogs. In vitro displacement studies demonstrated that iodoethylspiperone and iodoethylspiroxatrine have specific binding properties for the D2 and 5HT1A receptors respectively. Thus this method of synthesis seemed suitable to prepare new potential agents to study receptors.
Synthesis of high specific activity tritiated dihydropyridines: Nicardipine‐3H
Authors: Parnes Howard , Huan Glenn T.
Published: October 2006

The synthesis of high specific activity 3‐nitrobenzaldehyde‐[4,6‐3 H], a key intermediate in the general synthesis of tritiated 4‐aryldihydropyridines, is described. This substance was then used to prepare the calcium channel entry blocker, nicardipine‐[4′,6′‐3H] at a specific activity of 51 Ci/mmole via the Hantzsch process.
Synthesis of [methyl‐2H]‐labelled ajmalicine, yohimbine, tabersonine and catharanthine
Authors: Auriola S. , Naaranlahti T. , Lapinjoki S. P.
Published: October 2006

Deuterium labelled analogues of ajmalicine, yohimbine, tabersonine and catharanthine were synthesized by base catalyzed transesterification of the methyl group in deuterated methanol.
14C‐labelling of hematopoietic immunomodulator ( Z‐100 ) consisting of polysaccharides obtained from cultivation of Mycobacterium tuberculosis
Authors: Sano H. , Nagae H. , Suzuki M. , Tagashira E. , Fukasaku N. , Kimishima S. , Yugi H. , Baba S.
Published: October 2006

Mycobacterium tuberculosis was cultivated in sauton meium contaning 31.4 GBq of 14C‐glycerol as a source of carbon to obtain 14C‐labelled form of hematopoietic immunomodulator ( Z‐100 ). 14C‐Z‐100 was produced from the organisms with 0.11‐0.15 % of radiochemical yield. The specific radioactivity of 14C‐Z‐100 ranged from 3.3 to 7.5 kBq/eq.μ mole D‐arabinose. 14C‐Z‐100 was analyzed by gel filtration high performance liquid chromatography using a refractive index ( RI ) detector. The elution pattern of the polysaccharides of 14C‐Z‐100 agreed closely with thay of Z‐100, indicating that 14C‐Z‐100 was equivalent to Z‐100 in chemical properties In addition, the elution pattern obtained from the radioactivity of 14C‐Z‐100 was approximated to that obtained by using a RI detector, indicating that Z‐100 was generally labelled with 14C. Furthermore, 14C‐Z‐100 was confirmed to have almost the same interleukin‐3 inducing ability and antitumor activity as those of Z‐100.
Platinum‐catalyzed exchange labelling of representative organic compounds with tritium gas or tritiated water
Authors: Williams Philip G. , Lukey Christopher A. , Long Mervyn A. , Garnett John L.
Published: October 2006

A wide range of simple organic substrates has been successfully tritium labelled using reduced platinum oxide as catalyst. Exchange conditions involved reaction temperatures in the range 60–150°C, and reaction times of 3–7 days. The isotope sources for the reactions were tritium gas and tritiated water. Analysis of the labelled products was accomplished by radio‐glc and by 3H NMR spectroscopy. The specific activities ranged up to 1100 mCi/mL, and most of the labelled products showed high radiochemical purity. The regioselectivity of tritium incorporation, as obtained from 3H NMR studies, supports currently accepted theories for mechanisms of platinum‐catalyzed hydrogen isotope exchange. The results also show remarkable consistency for a heterogeneous system under widely varying reaction conditions.
Synthesis of a carbon‐14 labelled peptidyl carbamate human leukocyte elastase inhibitor and its immobilization on a tritiated water soluble polymer
Authors: Banks William R. , Rypacek Frantisek , Digenis George A.
Published: October 2006

A carbon‐14 labelled hemisuccinate peptidyl human leukocyte elastase inhibitor, p‐nitrophenyl‐N‐(1,4‐(14C)‐succinyl‐L‐alanyl‐L‐alanyl‐prolylmethyl‐ N‐isopropyl carbamate, and a tritium labelled hydrophilic polymer, poly‐α, β‐[N(2‐hydroxy‐1‐[3H]‐ethyl)]‐D,L aspartamide were prepared and are reported here. The immobilization of the [14C]‐peptidyl carbamate onto the tritiated polymer to afford a double labelled macromolecular inhibitor of human leukocyte elastase is also illustrated.
Synthesis of triple (13C2, 15N), single (14C), and double (14C2) labeled trimetrexate
Authors: Hicks James L. , Hartman Jon D. , Skeean Richard W. , Huang C. C. , Kepler John A. , Liang Chun‐Hua
Published: October 2006

A method was developed for the synthesis of triple (13C2, 14N) labeled trimetrexate. A method for single carbon‐14 labeled synthesis is also described. Modifications of the triple labeled synthesis with carbon‐14 produced a doubled carbon‐14 labeled trimetrexate.
Rapid synthesis of 14C forskolin by a route suitable for 11C labeling
Authors: Sasaki T. , Ogihara‐Umeda I , Nishigori H. , Ikegami S. , Senda M. , Kitani K. , Ogawa K. , Nozaki T.
Published: October 2006

Radiolabeled forskolin was synthesized by acetylation of deacetylforskolin with 14C‐labeled acetic acid in the presence of dicyclohexylcarbodiimide. Separation of labeled forskolin of greater than 97% radiochemical purity was achieved by HPLC with a reversed‐phase column. The synthesis and purification of labeled forskolin were achieved in less than 30 min and the radiochemical yield of labeled forskolin after HPLC purification was about 30%, These methods are therefore applicable for production of 11C‐forskolin which may be useful for PET second messenger imaging.
Preparation of 2‐[α‐(2‐ethoxyphenoxy)benzyl]‐[5‐14C]morpholine methanesulfonate ([14C]reboxetine) a new antidepressant agent
Authors: Angiuli Patrizia , Fontana Erminia , Vicario Gian Piero
Published: October 2006

The labelling with radiocarbon of the new antidepressant agent Reboxetine is described. The preparation has been carried out in a two step procedure using 2‐chloro‐N‐(3‐(2‐ethoxyphenoxy)‐2‐hydroxy‐3‐phenyl)propyl‐[1‐14C]acetamide 2 as starting material. The expected compound was prepared by cyclization of the above halogenoacylamido alcohol to the corresponding morpholone ring followed by reduction to the final [5‐14C]morpholone derivative 4, 98% radiochemically pure and with specific radioactivity of 988 MBq/mmol. An overall radiochemical yield of 57.5% was achieved.
Synthesis of [O‐14CH3] sinapic acid
Authors: Barthes Pascale , Duran Hubert , Gorrichon Liliane
Published: October 2006

[O‐14CH3] Sinapic acid was synthesized with a specific activity of 54 mCi/mmol. Radiolabelled was carried out on methyl‐3‐(4‐benzyloxy 3‐hydroxy 5‐methoxy phenyl) 2‐propenoate with high yield, the deprotection of phenolic function and acid function are quantitative.
Synthesis of carbon‐14 labelled CD 271 (6‐[3‐(1‐adamantyl)‐4‐methoxyphenyl]‐2‐naphthoic acid) a potential new agent for dermatology
Authors: Pilgrim W. R. , Nedoncelle P. , Frideling J‐P. , Shroot B.
Published: October 2006

6‐[3‐(1‐Adamantyl)‐4‐methoxyphenyl]‐2‐naphthoic acid (1), a promising new compound for the treatment of disorders of keratinization, has been synthesized in [14C]‐labelled form from barium [14C]‐carbonate via labelled benzene. Benzene‐[U‐14C] was converted to 4‐bromo‐methoxybenzene‐[phenyl‐U‐14C] in six steps. Introduction of the adamantyl ring was carried out using 1‐acetoxyadamantane under acid catalysis. 2‐(1‐Adamantyl)‐4‐bromo‐methoxybenzene‐[phenyl‐U‐14C] (2) was converted to a zincate and coupled with methyl 6‐bromo‐2‐naphthoate using a nickel catalyst. The product of the aryl coupling reaction (3) was then saponified to give 6‐[3‐(1‐adamantyl)‐4‐methoxyphenyl‐[phenyl‐U‐14C]]‐2‐naphthoic acid.
An improved synthesis of labelled fatty acid carboxamides. N ‐phenyl [9,10(n)‐3H] oleamide and N ‐[ring‐G‐13C6] phenyloleamide as standards for spanish toxic oil syndrome studies
Authors: Casas Josefina , Messeguer Angel
Published: October 2006

A one‐pot procedure for the high yield preparation of title compounds is reported. The key features involve the conversion of the fatty acid into the corresponding mixed anhydride by reaction with ethyl chloroformate, followed by reaction with aniline, using acetonitrile as solvent to ensure homogeneous reaction mixtures and keeping reaction times short to avoid the formation of undesirable side products.
Synthesis of 4‐amino‐5‐chloro‐N[2‐(diethylamino)ethyl]‐2‐ [(butan‐2‐on‐3‐yl)oxy]‐[carbonyl‐14C]benzamide hydrochloride (14C‐batanopride)
Authors: Standridge R. T. , Swigor J. E.
Published: October 2006

The title compound (1) was synthesized by a 7‐step sequence. 4‐Amino‐2‐hydroxy‐[carbonyl‐14C]benzoic acid (1) was selectively methylated to provide the ether ester 2, which was smoothly chlorinated in acetic acid to give 3. The ester was hydrolyzed with aqueous potassium hydroxide to the amino acid 4. This reachted readily, as a mixed anhydride, with diethylaminoethylamine, yielding [14C]‐metoclopramide (5). Sodium ethanethiolate in dimethylformamide cleaved the methoxy group cleanly to the phenol (6); this material was not isolated but was condensed in situ with 3‐chloro‐2‐butanone, yielding 7. Formation of the salt with concentrated hydrochloride acid in acetone provided the title compound (8), having a radiochemical purity of 95.6% and a specific activity of 29.8 μCi/mg.
A general approach to the synthesis of 14C‐labeled photoactive acrylic acids
Authors: Mohammad Taj , Morrison Harry
Published: October 2006

Condensation of aromatic carboxaldehydes with [2‐14C]‐malonic acid under Knoevenagel conditions provides corresponding β‐aryl substituted [α‐14C]‐acrylic acids. The reaction is applicable to both aromatic and heteroaromatic aldehydes under controlled reaction conditions leading to moderate to good yields.
Preparation of the antioestrogenic compound N‐[methyl‐11C]‐toremifene for the study of oestrogen‐receptor positive tumors in vivo
Authors: Någren Kjell , Takahashi Toshihiro , Lehikoinen Pertti , Bergman Jörgen
Published: October 2006

The synthesis of the antioestrogenic compound N‐[methyl‐11C]toremifene (N‐[methyl‐11C]‐(Z)‐2‐(4‐(4‐chloro‐1,2‐diphenyl‐1‐butenyl)‐ phenoxy)‐N,N‐dimethylethylamine) by alkylation with [11C]methyl iodide of the desmethyl precursor, generated in situ from the corresponding citrate with 2,2,6,6‐tetramethylpiperidine (TMP), is reported. The reaction product was purified with high performance liquid chromatography (HPLC) using either normal or reversed phase conditions. After solubilization by sonication in citric acid / propylene glycol / water the chemically and radiochemically pure product was obtained in 55–65 % radiochemical yield (decay corrected from [11C]methyl iodide) in 40–45 min after end of bombardment (EOB).
Tritium labelling of nitroaryldihydropyridines
Authors: Pleiß Ulrich , Schmitt Peter
Published: October 2006

The synthesis of tritium labelled nitroaryldihydropyridines was achieved by dehalogenation of a brominated precursor using the palladium hydroxide on charcoal as catalyst. The investigations described show the example [3H]nimodipine which was prepared with a specific activity of 16,4 Ci/mmol (607 GBq/mmol).
Syntheses of di‐tritiated 9(O)‐methano‐Δ6(9α)‐prostaglandin I1 methyl esters
Authors: Manabe Kenji , Tanaka Toshio , Kurozumi Seizi , Kato Yoshinori
Published: October 2006

Two di‐tritiated isocarbacyclin [9(O)‐methano‐Δ6(9α)‐prostaglandin I1] methyl esters 5, 10 were synthesized from (Z)‐olefinic precursors 23, 31 at ω‐side chain by catalytic hydrogenation with tritium gas, respectively. These substances 5, 10 having high specific activities can be used for the pharmacokinetics and metabolism studies of 9(O)‐methano‐Δ6(9α)‐prostaglandin I1 methyl ester 2 and its (17S)‐17,20‐dimethyl derivatives 7.
The labelling of 2‐oxoquazepam with electrophilic 18F
Authors: Duelfer T. , Johnström P. , Stone‐Elander S. , Holland A. , Halldin C. , Haaparanta M. , Solin O. , Bergman J. , Steinman M. , Sedvall G.
Published: October 2006

2‐Oxoquazepam, 7‐chloro‐1‐(2,2,2‐trifluoroethyl)‐1,3‐dihydro‐5‐(2‐fluorophenyl)‐2H‐1,4‐benzo‐diazepine‐2‐one, is a benzodiazepine agonist. It has been shown to bind in vitro with a higher affinity to benzodiazepine type 1 receptors than to type 2 receptors. Here we report the synthesis of a trimethyltin precursor and demonstrate the feasibility of using it for radiolabelling acid‐ and base‐sensitive benzodiazepine structures such as 2‐oxoquzepam. Conversions of the electrophilic fluorine to [18F]‐2‐oxoquazepam on the order 20–25% were obtained.
Isotopically labelled adenosine triphosphate analogues: Synthesis of [6‐15N]‐ adenylyl imidodiphosphate and [6‐15N]‐adenylyl methylenediphosphonate
Authors: Sarfati S. R. , Pochet S.
Published: October 2006

We report the synthesis of [6‐15N]‐labeled‐AMP following a novel route from adenosine with an overall yield (12%) better than with a previously described procedure from inosine (6%). The two analogues of [6‐15N]‐adenosine triphosphate, adenylyl imidodiphosphate (AMP‐PNP) and adenylyl methylenediphosphonate (AMP‐PCP), were prepared from labeled AMP.
Synthesis of [3H]naltrindole [1]
Authors: Dorn Clifford R. , Markos Charles S. , Dappen Michael S. , Pitzele Barnett S.
Published: October 2006

[3H]Naltrindole ([3H]1) was prepared for use as a selective radiolabeled ligand for delta opioid receptors. The Fischer indole synthesis from naltrexone and 2,4‐dibromophenylhydrazine produced dibromide precursor 2, which was catalytically dehalogenated with carrier free tritium gas to afford [3H]1 in 45.8% yield at a specific activity of 39.5 Ci/mmol.
Synthesis of (1R)‐(1‐acetamido‐2‐phenylethyl)boronic acid‐1‐13C
Authors: Matteson Donald S. , Michnick T. John
Published: October 2006

(1R)‐(1‐Acetamido‐2‐phenylethyl)boronic acid‐1‐13C, which is the boron analogue of N‐acetylphenylalanine, has been synthesized via a modification of the route previously established for the unlabelled compound. The 13C label is derived from dichloromethane‐13C. The previous conditions utilized excess dichloromethane, but it has now been found that a stoichiometric amount of dichloromethane suffices for the preparation of (dichloromethyl)lithium and its reaction with a boronic ester. Thus, the method has broad potential for the synthesis of compounds bearing 13C lebels at chiral sites. The 1H and 13C NMR spectra of the target compound and the intermediates leading to it are discussed.
Preparation of pyridostigmine bromide labeled with carbon‐14 and tritium1
Authors: Kepler J. A. , Twine C. E. , Austin R. D.
Published: October 2006

[2‐14C]Pyridostigmine bromide was prepared in 17.6% radiochemical yield with specific activity of 18 mCi/mmol. The reaction sequence involved preparation of 2‐furan[14C]carboxylic acid by carbonation of 2‐lithiofuran, followed by conversion to 2‐amino[14C]methyl furan by lithium aluminum hydride reduction of its carboxamide. Oxidative rearrangement of 2‐amino[14C]methylfuran gave 3‐hydroxy[2‐14C]pyridine which was converted to [2‐14C]pyridostigmine bromide by reaction with dimethylcarbamyl chloride and quarternization with bromomethane. Pyridostigmine bromide labeled in the methyl group of the carbamate function was prepared in 73% yield with specific activity of 37.6 mCi/mmol by reaction of bis‐3‐pyridyl carbonate with [14C]dimethylamine followed by quarternization with bromomethane. [6‐3H]‐Pyridostigmine bromide with specific activity of 22.5 mCi/mmol was prepared by catalytic halogen‐tritium replacement of 2,6‐dibromo‐3‐dimethylcarbamyloxypyridine followed by quarternization with bromomethane and back‐exchanging the labile 2‐tritium.
Synthesis of tritium‐labelled imipramine and desipramine with high specific activities
Authors: Yakovleva L. A. , Kaminski Ju. L. , Sosnova L. P. , Kudelin B. K.
Published: October 2006

[G‐3H]imipramine and [G‐3H]desipramine with specific activities 110–160 and 80–100 kCi/mol, respectively were synthesized by high temperature solid‐phase catalytic isotope exchange with gaseous tritium.
Use of HPLC for increasing the molar specific activities of tritium‐labelled nucleosides
Authors: Kudelin B. K. , Gavrilina L. V. , Kaminski Yu. L.
Published: October 2006

The possibility of chromatographic separation of different isotopic forms of tritiated nucleosides has been demonstrated. Using a reversed‐phase column in 3–5% solutions of ethanol in water the labelled nucleosides eluted ahead of corresponding unlabelled analogs. Such isotope effects allow simultaneous fine purification of nucleosides and its fractionation according to molar specific activity value.
Synthesis of an iodine‐125‐labeled retinoid
Authors: Dawson Marcia I. , Hobbs Peter D. , Rhee Sung W.
Published: October 2006

The carrier‐free synthesis of 4‐(5′,6′,7′,8′‐tetrahydro‐4′‐[125I]iodo‐5′,5′,8′,8′‐tetramethyl‐2′‐anthracenyl)benzoic acid (4′‐[125I]TTAB) is described. Site specific radioiodination was accomplished by electrophilic destannylation of the tri(n‐butyl)tin analog of the retinoid with Na125I and chloramine‐T. 4′‐[125I]TTAB (33 μCi, 1.65% radiochemical yield based on Na125I consumed) was purified by reversedphase HPLC.
Synthesis of [2,3,4,5‐14C]‐1‐vinyl‐2‐pyrrolidinone
Authors: Digenis George A. , McClanahan J. S. , Chen Pei‐Lin
Published: October 2006

An efficient small scale synthesis of 14C labeled 1‐vinyl‐2‐pyrrolidinone (NVP) is described. The cyclization of commercially available [1,2,3,4‐14C]‐γ‐aminobutyric acid (GABA) gives [2,3,4,5‐14C]‐2‐pyrrolidinone which is vinylized with vinyl acetate via a sodium tetrachloropalladate catalyst to give good yields of [2,3,4,5‐14C]‐1‐vinyl‐2‐pyrrolidinone.
Synthesis of cyano‐[D11]‐cyclohexane
Authors: Abenhaim D. , Loupy A. , Petit A. , Gonthier‐Vassal A. , Szwarc H.
Published: October 2006

Cyano‐[D11]‐cyclohexane was prepared from commercial [D12]‐cyclohexanol via the sequence alcohol‐chloride‐acid‐nitrile in an overall yield of 33% after purification. Isotopic purity was at least 98%.
Synthesis of 9‐[3‐pyridylmethyl]‐9‐deazaguanine[2‐14carbon]
Authors: Pathak Ved P. , Montgomery John A.
Published: October 2006

14C labeled 2‐amino‐7‐(3‐pyridylmethyl)‐4‐oxo‐3H,5H‐pyrrolo[3,2‐d]pyrimidine(6) was synthesized starting from methyl 3‐amino‐4‐(3‐pyridylmethyl)‐1H ‐pyrrolo‐2‐carboxylate. This pyrrole on condensation with 14C labeled benzoylisothiocyanate followed by methylation gave methyl 3‐[N‐benzoyl‐S‐methylisothiocarbamoyl)‐amino]‐4‐(3‐pyridylmethyl)‐1H‐pyrrole‐2‐carboxylate [3‐14C] (5), which on reaction with methanolic ammonia furnished the title compound(6).
Synthesis of 7‐3H‐(IS, 4S)‐4‐(3,4‐dichlorophenyl)‐1,2,3,4‐tetrahydro‐N‐methyl‐I‐I‐naphthalenamine hydrochloride (7‐3H‐Sertraline)
Authors: Welch Willard M. , Williams Michael T.
Published: October 2006

The preparation of the title compound, a selective serotonin uptake inhibitor with antidepressant properties in man, is described. The preparation of the 7‐bromo precursor via a stereoselective seven‐step sequence from (1R)‐7‐bromo‐1,2,3,4‐tetrahydro‐N‐methyl‐1‐naphthalenamine is described. The radiochemical purity of the product obtained after reduction with tritium was greater than 99 % and the specific activity was 17.6 Ci/mM.
Synthesis of [2‐14C] griseolic acid 9′‐(4‐acetoxy‐3‐methoxybenzyl)ester, a antiglaucoma agent
Authors: Sato Susumu , Mikoshiba Isamu , Kawai Kenji , Hirai Koichi
Published: October 2006

Starting from [14C] ethyl orthoformate and amidine derivative 3 derived from griseolic acid in 6 steps, the synthesis of [2‐14C] griseolic acid 9′‐(4‐acetoxy‐3‐gethoxybenzyl)ester [14C]‐2, a promising antiglaucoma agent with its regioisomer [2‐14C] griseolic acid 8′‐(4‐acetoxy‐3‐gethoxybenzyl)ester 9 and [2‐14C] griseolic acid [14C]‐1 has been achieved.
Synthesis of [14α‐methyl‐3H]‐24,25‐dihydrolanosterol
Authors: Dekeczer Steve , Kertesz Denis , Parnes Howard
Published: October 2006

We describe, herein, the first synthesis of isomerically pure title compound (6) at high specific activity. This required the development of a convenient, regiospecific synthesis of the Δ8(9)‐15‐ketone (15) and subsequent alkylation with methyl‐[3H3] iodide. A key step in our procedure was the use of an electrochemical reduction of the intermediate [14α‐methyl‐3H]‐ 15‐oxo ‐dihydrolanosterol (19). This process was effected cleanly and in high yield to give (6), an important assay tool in the search for cholesterol lowering agents. This approach was found to be significantly superior to the Wolff‐Kishner reduction of the corresponding 3‐benzoate (18).
Synthesis of 14C labelled electrophilic ligands of the colchicine binding site of tubulin: Chloroacetates of demethylthiocolchicines and of N‐acetylcolchinol; isothiocyanate of 9‐deoxy‐N‐acetylcolchinol
Authors: Boyé Olivier , Getahun Zelleka , Grover Surinder , Hamel Ernest , Brossi Arnold
Published: October 2006

14C‐Chloroacetates of 2‐demethylthiocolchicine 7 (specific activity 55.0 mCi/mmol, radiochemical yield 26.1%), and of 3‐demethylthiocolchicine 8 (specific activity 55.0 mCi/mmol, radiochemical yield 5.7%) were synthesized and found to covalently bind with high specificity to the β‐subunit of tubulin. The 14C‐chloroacetate of N‐acetylcolchinol 5 (specific activity 56.0 mCi/mmol, radiochemical yield 7.8%) and the 14C‐isothiocyanate 6 (specific activity 50.0 mCi/mmol, radiochemical yield 32%) were also prepared and found to react covalently with tubulin but in a nonspecific manner. With the radiolabelled chloroacetates 7 and 8 two compounds are now available to further characterize the colchicine binding site on the β subunit of tubulin.
133Ba cryptate labeled immunoglobulin G
Authors: Pettit William A. , Swailes Barbara K.
Published: October 2006

A method for the attachment of cryptates containing radioactive metal ions to proteins has been developed. The aminocryptand, 4,7,13,16,21,24‐hexaoxa‐5,6‐(4′‐aminobenzo)1,10‐diazabicyclo[8.8.8]‐hexacosane, was complexed with divalent 133Ba and subsequently converted to the isothiocyanatocryptate. The bioconjugate with immunoglobulin G was formed in better than 40% radiochemical yield in a three step procedure. Alternatively, the radiolabeled bioconjugate could be formed by addition of 133Ba to immunoglobulin G that had been reacted with the isothiocyanate derivative of the cryptand. Stability studies indicated the radiolabeled bioconjugate has a half‐life of 6 h and 12 h in phosphate buffers of pH=7.4 and pH=9.2, respectively. Attempts to label the immunoglobulin with the corresponding 142Pr cryptate resulted in considerable radioactive colloid formation with no detectable bioconjugate produced.
Synthesis of tritium labelled mometasone furoate
Authors: Hesk D. , Delduca P. , Koharski D. , McNamara P. , Magatti C. , Saluja S. , Thomas L.
Published: October 2006

3H‐mometasone furoate was synthesized by a six step procedure. The label was introduced via the reduction and re‐oxidation of the 1,2 double bond in the A ring. The remaining 4 steps were accomplished with on overall radiochemical yield of 28%. Analysis by 3H nmr indicated that most of the label (≈95%) was located in the 2‐position and the remainder in the 1‐position.
Technetium‐99m‐dimethylglyoxime (99mTc‐DMG) as renal imaging agent
Authors: Adonaylo Viviana N. , Stahl Adriana , Cañellas Carlos O. , Pomilio Alicia B. , Vitale Arturo A.
Published: October 2006

Dimethylglyoxime (DMG) labelled with 99mTc is here presented as a renal imaging agent. The behaviour of this complex was analysed at different pH by means of UV spectral data and using DMG‐calcium chloride as a reference complex. Biokinetic data were evaluated in two biological models, Sprague‐Dawley rats and Didelphis albiventris argentine opossum. Biodistribution in rats demonstrated fast and specific renal excretion. Time‐activity vabues over both kidneys could be quantified for this complex. Renographic studies led to mean time‐to maximum values on twelve assays of 2.0 ± 0.1 min and a mean relative function of 53.0 ± 2.3 and 47.0 ± 3.2 for right and left kidneys, respectively. 99mTc‐DMG showed specificity for the renal excretion pathway and therefore Seems to be a very useful radiopharmaceutical for renal function studies.
Synthesis of14C‐labeled hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine(RDX)
Authors: Horváth Károly , Alworth William L.
Published: October 2006

14C‐labeled hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (2, RDX) was prepared by nitrolysis of hexahydro‐1,3,5‐tripropionyl‐1,3,5‐triazine (1) for bioenvironmental studies. 1 was synthesized from paraformaldehyde and propionitrile by a modified method reported earlier.
Synthesis of the angiotensin converting enzyme inhibitor 3H‐RAC‐X‐65
Authors: Chung A. Y. K. , Ryan J. W. , Groves W. E. , Valido F. A. , Berryer P.
Published: October 2006

We prepared the angiotensin converting enzyme (ACE) inhibitor N‐[1(S)‐carboxy‐3‐(4′‐3H)carboxanilidopropyl]‐L‐Ala‐L‐Pro (3H‐RAC‐X‐65). The triflate of D‐(+)‐lactic acid benzyl ester was reacted with N′‐(4‐iodophenyl)‐L‐glutamine methyl ester. The benzyl ester was removed with HF, and the free carboxyl group was coupled to L‐proline methyl ester via diphenylphosphorylazide. Methyl ester groups were removed by saponification. The product was dehalogenated in 10 Ci of 3H2 to yield 3H‐RAC at 24.3 Ci/mmole (89.7% yield). 3H‐RAC‐X‐65 was indistinguishable from its unlabeled counterpart in its ability to inhibit ACE and enter into a tightly bound enzyme:inhibitor complex.
Synthesis of N1‐3‐[18F]fluoropropyl‐N4‐2‐([3,4‐dichlorophenyl]ethyl)piperazine, a high affinity ligand for sigma receptor
Authors: Kiesewetter Dale O. , de Costa Brian
Published: October 2006

The radiochemical synthesis of the high affinity, selective sigma receptor ligand, N1‐3‐[18F]Fluoropropyl‐N4‐2‐([3,4‐dichlorophenyl]ethyl)piperazine, is reported. The labeled compound is prepared by fluoride displacement on a bismethanesulfonate salt of the propyl methanesulfonyloxy precursor. The product is isolated by first passage through a BONDELUT‐SI and subsequently HPLC in high radiochemical and chemical purity with a decay corrected radiochemical yield of 49 ± 9%.
Synthesis of [14C]‐labelled 3‐[N‐(4‐bromophenyl)carbamoyl]‐7‐chloro‐4‐hydroxycoumarin and 3‐[N‐[5‐(trifluoromethyl)‐1,3,4‐thiadiazol‐2‐yl]carbamoyl]‐7‐chloro‐4‐hydroxycoumarin
Authors: Lee Byung H. , Clothier Michael F.
Published: October 2006

The novel [14C]‐labelled 3‐carbamoyl‐4‐hydroxycoumarins were prepared in two steps from 4‐chloro‐acetylsalicyloyl chloride (3). The isotope was incorporated by the reaction of diethyl malonate‐1,3‐14C with 4‐chloro‐acetylsalicyloyl chloride (3). Subsequent condensation of the resulting 3‐ethoxycarbonyl‐4‐hydroxy‐7‐chlorooumarin (5a) with 4‐bromo‐aniline gave 3‐[N‐(4‐bromophenyl)carbamoyl‐7]‐chloro‐4‐hydroxycoumarin (1a) with a specific activity of 0.7 mCi/mmol. Condensation of (5a) with 2‐amino‐5‐trifluoromethyl‐1,3,4‐thiadiazole gave 3‐[N‐[5‐(trifluoromethyl)‐1,3,4‐thiadiazol‐2‐yl]carbamoyl]‐7‐chloro‐4‐ hydroxycoumarin (2a) with a specific activity of 0.6mCi/mmol.
A synthetic approach to carbon‐14 labeled anti‐bacterial napthyridine and quinolone carboxylic acids
Authors: Ekhato I. Victor , Huang Che C.
Published: October 2006

Labeled versions of (S)‐clinafloxacin (1) and two naphthyridine carboxylic acid anti‐bacterial compounds 2 and 3 which are currently in development were synthesized. Preparations started from hitherto unknown bromo compounds 22 and 10, from which the corresponding 14C‐labeled aromatic carboxylic acids 23 and 12 were generated by metal‐halogen exchange followed by carboxylation reaction. Details of these preparations are given.
Synthesis of [5‐14C]‐dodecane and [8‐14C]‐hexadecane
Authors: Schenk Torsten , Schmidt Burkhard
Published: October 2006

[5‐14C]‐Dodecane and [8‐14C]‐Hexadecane were synthesized starting with [1‐14C]‐octanoic acid. The carboxylic acid was reduced to 1‐octanol, which was esterified to n‐octyl p‐toluenesulfonate. Following a Corey‐House procedure, the sulfonate was either reacted with Li[Cu(butyl)2] to [5‐14C]‐dodecane (40 % overall yield), or with Li[Cu(octyl)2] to [8‐14C]‐hexhadecane (24 % overall yield). The lithium di‐alkyl cuprates were prepared from butyl lithium and n‐octyl bromide, respectively. Preliminary experiments with non‐labeled compounds using a wittig reaction as chain extension step, turned out to be less favourable. The Corey‐House route provides a simple method for the synthesis of specifically 14C‐labeled alkanes from commercially available [1‐14C]‐carboxylic acids.
Preparation of 1,2‐dimethoxy‐4‐(bis‐diethylaminoethyl‐[14C]‐amino)‐5‐bromobenzene
Authors: Wang Theodore S. T. , Fawwaz Rashid A , van Heertum Ronald H.
Published: October 2006

1,2‐Dimethoxy‐4‐(bis‐diethylaminoethyl‐[14C]‐amino)‐5‐bromobenzene (III) was synthesized for in vivo pharmacokinetic and pharmacodynamic evaluation. The synthesis of (III) was easily obtained by the direct alkylation of 1,2‐dimethoxy‐5‐bromo‐aniline with beta‐diethylaminoethyl chloride‐ethylene‐[14C], using CH3MgCl as the proton abstractor. Compound III was obtained with a 22.3% yield. The specific activity was 2.2mCi/mmol, with a radiochemical purity of >99%.
Synthesis of deuterium‐labelled diclofenac sodium
Authors: Leroy D. , Richard J. , Godbillon J.
Published: October 2006

Diclofenac sodium labelled with deuterium in the phenylacetic ring was prepared from [2H5]‐bromobenzene in a six‐step reaction. It was found to be suitable for use in pharmacokinetic and bioavailability studies in man.
Synthesis of a tritium labelled azaspirane: SK&F 105685
Authors: Landvatter Scott W. , Senderoff Stephen G. , Heys J. Richard
Published: October 2006

SK&F 105685 (1) was prepared in tritium labelled form by two different methods. Moderate specific activity material was obtained via sodium borotritide reduction on an iminium perchlorate precursor which itself had been derived from 1. High specific activity material was obtained via catalytic reduction of a terminal double bond.
Synthesis of carbon‐14 labelled piritrexim ‐ a potential anticancer agent
Authors: Hill John A. , Wisowaty James C. , Darnofall Michael E.
Published: October 2006

Piritrexim 1(2,4‐diamino‐6‐(2,5‐dimethoxybenzyl)‐5‐methylpyrido[2,3‐d]‐pyrimidine) was synthesized in the [14C]‐labelled form with specific activity 50.8 mCi/mmol suitable for drug metabolism, transport, dispostion and mechanism of action studies. The synthetic sequence involved synthesis of the novel 2‐bromo‐5‐(2,5‐dimethoxybenzyl)‐4‐methyl‐3‐pyridinecarbonitrile and condensation of this compound with [14C]‐guanidine hydrochloride. The radiochemical purity was >98%.
The synthesis and separation of [3‐2H]tropine and [3‐2H]pseudotropine (ψ‐tropine)
Authors: Bartholomew Barbara A. , Smith Michael J. , Darcy Paul J. , Trudgill Peter W. , Hopper David J.
Published: October 2006

Tropinone was reduced using sodium borodeuteride to give a mixture of the epimers [3‐2H] tropine and [3‐2H]pseudotropine with the latter compound predominating and constituting about 70% of the mixture. Crystallisation of the product from diethyl ether gave crystals of pure [3‐2H]pseudotropine and a supernatant solution containing a mixture of the epimers. Acetylation of this mixture using acetyl chloride preferentially acetylated the pseudotropine and the acetylated products were separated from the tropine by flash chromatography to leave a sample of pure [3‐2H]tropine.
Enzymatic synthesis of tritium — labelled prostaglandin D2 and its conversion to other prostaglandins
Authors: Shram Stanislav I. , Lazurkina Tatyana Yu. , Shevchenko Valerii P. , Nagaev Igor Yu. , Myasoedov Nikolai F.
Published: October 2006

The one‐stage enzymatic synthesis of tritium‐labelled prostaglandin D2 from labelled arachidonic acid was performed by using the enzyme system PGH‐synthetase/PGH‐PGD‐isomerase. By enzymatic and chemical transformation of [3H]PGD2 the following compounds were obtained: 15‐keto‐13,14‐dihydro‐[3PGD2, 9α,11β‐[3H]PGD2, 9‐deoxy‐Δ9‐[3H]‐PGD2 ([3H]PGJ2) and Δ12‐13,14‐dihydro‐[3H]PGJ2. It was found that L‐selectride is a more effective reducing agent than sodium borohydride in the synthesis of 9α,11β‐[3H]PGF2.
Directed lithiation of 3,5‐dichloroaniline and its application in the synthesis of 1,3‐dichloro‐6,7,8,9,10,12‐hexahydroazepino[2,1‐b][5‐14C]quinazoline monohydrochloride
Authors: Ekhato I. Victor , Huang Che C.
Published: October 2006

1,3‐Dichloro‐6,7,8,9,10,12‐hexahydroazepino[2,1‐b][5‐14C]quinazoline monohydrochloride (1) was synthesized in 12% overall yield starting from 3,5‐dichloroaniline, and a radiochemical purity of 99.6% was obtained. The synthetic sequence was facilitated by the regio‐controlled preparation of 4,6‐dichloroanthranilic acid (3) from 3,5‐dichloroaniline using the t‐butoxycarbonyl‐protected aniline and t‐butyllithium/tetramethylethylenediamine (t‐BuLi/TMEDA) combination followed by carboxylation. The quinazoline monochloride 1 was constructed by condensation of 3 with 1‐aza‐2‐methoxyl‐cycloheptene and then reduction.
Tritium gas exchange studies of platinum‐loaded microporous aluminophosphate molecular sieves
Authors: Long Mervyn A. , Than Chit
Published: October 2006

Platinum‐loaded microporous aluminophosphate molecular sieves (Pt‐AlPO4‐5) were synthesized and studied as catalysts for promoting tritium isotope labelling by exchange between tritium gas and aromatic, heteroaromatic and aliphatic hydrocarbons. The presence of the Pt metal considerably enhanced the activation of the tritium gas. Detailed isotope orientation patterns, as determined by 3H nmr spectroscopy, showed that the AlPO4‐5 component of the catalyst dominated the exchange reactions, but some influence of the Pt metal was apparent with some substrates.
Synthesis of [3H]FPL 64176, a potent calcium channel activator
Authors: Foged Christian , Madsen Peter
Published: October 2006

Tritium labelled FPL 64176 (1, methyl 2,5‐dimethyl‐4‐2‐(phenylmethyl)benzoyl]‐1H‐pyrrole‐3‐carboxylate), a potent calcium channel activator with insulinotropic properties was synthesized from the corresponding bromo derivative (3) using tritium gas and Pd/C catalyst. (3) was in turn prepared from methyl 2,5‐dimethylpyrrole‐3‐carboxylate (4) in a one pot procedure. The specific activity of [3H]FPL 64176 was 38 mCi/mmol and radiochemical purity >98%.
Synthesis of a 125I labelled azido‐substituted glibenclamide analogue for photoaffinity labelling of the sulfonylurea receptor
Authors: Chudziak Franz , Schwanstecher Mathias , Laatsch Hartmut , Panten Uwe
Published: October 2006

N‐{4‐(2‐{4‐Azido‐2‐hydroxy‐5‐[125I]iodobenzamido}ethyl)benzenesul]‐N′‐cyclohexylurea has been prepared as a novel photoaffinity ligand for the sulfonylurea receptor. This involved synthesis of a 4‐azidosalicyloyl analogue of glibenclamide and treatment of the analogue with Na125I and chloramine‐T. Purification by HPLC gave the radiolabelled sulfonylurea in 56% radiochemical yield and high specific activity (2130 Ci/mmol).
Synthesis of [11C]cyanoalkyltriphenylphosphoranes via [11C]cyanide substitution on haloalkylphosphonium salts
Authors: Hörnfeldt Katarina , Långström Bengt
Published: October 2006

The synthesis of the 11C‐labelled bifunctional precursors 3‐[11C]cyanoethyltriphenylphosphonium bromide (1′), 4‐[11C]cyanopropyltriphenylphosphonium bromide (2′), 5‐[11C]cyanobutyltriphenylphosphonium bromide (3′), 4‐[11C]cyanobutyltriphenylphosphonium iodide (4′) and 5‐[11C]cyanobutyltriphenylphosphonium iodide (5′) is presented. The label was introduced using [11C]cyanide in a substitution reaction on the ω‐haloalkyltriphenylphosphonium salt (bromide or iodide salt). The phosphonium salts 1′ −5′ were formed in 33–99% radiochemical yield in 5–10 min reaction time. After addition of epichlorohydrin as generator of base, the precursors 1–3 were formed. The potential of the intermediates 1–3 in Witting reactions was shown in model reactions with aromatic and aliphatic aldehydes. The aromatic olefins obtained from 1′–5′ were formed in 85–96 % radiochemical yield, with Z/E ratios between 67/33–75/25. The aliphatic olefins were obtained in 60–78% radiochemical yield from 4′ and 5′. In the reaction with 1′ and an aliphatic aldehyde, the yield decreased to 5–10%. The Z/E ratios were 100/0 for the aliphatic olefins. In an experiment starting with 2,7 GBq (73 mCi) hydrogen [11C]cyanide, 451 MBq (12.2 mCi) olefin from 3′ and 4‐nitrobenzaldehyde was obtained in 44 min from hydrogen [11C]cyanide production, with a 55 % decay corrected radiochemical yield, the radiochemical purity was 96%.
Facile radiolabelling and purification of 2β‐[O‐11CH3]‐carbomethoxy‐3β‐aryltropanes: Radiotracers for the dopamine transporter
Authors: Wilson Alan A. , Dasilva Jean N. , Houle Sylvain
Published: October 2006

Two potent dopamine transporter ligands, 2β‐[O‐11CH3]‐carbomethoxy‐3β‐(4‐methylphenyl)tropane and its 4‐chlorophenyl analogue, were synthesized by O‐alkylation at the 2β‐carboxy position with [11C]‐iodomethane. Separation of the [11C]‐labelled tropane from excess carboxylic acid precursor was readily achieved by semipreparative HPLC providing pure radiotracers at high specific activities (800–3000 mCi/μmole) suitable for in vivo PET studies. Radiosynthesis of this class of compounds by [O‐11CH3]‐methylation offers advantages over previously reported [N‐11CH3]‐methylation methods.
Preparation and quality control of 211At‐labelled and 125I‐labelled monoclonal antibodies. Biodistribution in mice carrying human osteosarcoma xenografts
Authors: Larsen Roy H. , Hoff Per , Alstad Jorolf , Bruland Øyvind S.
Published: October 2006

Two anti‐osteosarcoma monoclonal antibodies (TP‐3 IgG and TP‐1 F(ab′)2) were labelled with the α‐particle emitting radionuclide 211At and, for comparison of stability, with 125I using the N‐succinimidyl‐3‐(trimethylstannyl)benzoate intermediate. The quality of the final preparations was measured with immunoreactivity analyses using intact osteosarcoma cells. Immunoreactivity was well retained with values in the range of 65% to 85% for 211At‐labelled and 125I‐labelled TP‐3 IgG and approximately 60% for both 211At‐labelled and 125I‐labelled TP‐1 F(ab)2. Tumour uptake and retention as well as normal tissue distribution in mice with osteosarcoma xenografts were measured. The uptake of the two radionuclides in tumour was similar, while there was a slight general increase in normal tissue activity at later points for the 211At‐labelled MoAbs compared to the 125I‐labelled MoAbs, probably caused by a minor release of free 211At from the MoAb preparations. The stable retention in tumor tissue demonstrated in this study indicates that 211At‐labelled MoAbs may have potential in the treatment of tumours that allow a rapid uptake.
Preparation of deuteriated benzylamines and phenethylamine with raney alloys in an alkaline deuterium oxide solution
Authors: Tsukinoki Takehito , Tsuzuki Hirohisa , Ishimoto Keiko , Nakayama Kouji , Kakinami Takaaki , Mataka Shuntaro , Tashiro Masashi
Published: October 2006

Benzyl‐α,α‐2H2‐amine, 2‐2H1‐Benzyl‐α,α‐2H2‐amine, 3‐2H1‐Benzyl‐α,α‐2H2‐amine, 4‐2H1‐Benzyl‐α,α‐2H2‐amine, 2, 5‐2H2‐Benzyl‐α,α‐2H2‐amine, and phenethyl‐α,α,β,β‐2H4‐amine were prepared in high isotopic purities from the corresponding benzonitrile, bromobenzonitriles, and phenylacetonitrile by reduction with Raney Cu‐Al alloy in an alkaline deuterium oxide solution.