bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of high specific activity 80mBr and 123I labeled 5‐halodeoxyuridines and other 80mBr compounds for the study of auger electron toxicity
Authors: Mease Rc , Gatley Sj , Friedman Am
Published: October 2006

Convenient preparations of 80mBr and 123I‐labeled 5‐halodeoxyuridines, required for basic investigations of Auger electron radiotoxicity, are described. These radioactive thymidine analogs were synthesized from deoxyuridine, radiohalide and N‐chlorosuccinimide in dilute sulfuric acid. Yields were 50–60% for 80mBr and 60–70% for 123I. Apparent specific radioactivities (based on UV absorption under the radioactive HPLC peaks) were 150–550 Ci/mmol and over 2000 Ci/mmol for 80mBr and 123I, respectively. 5‐[80mBr]bromouracil was produced in 89% yield when uracil was used. [80mBr]Bromoantipyrine was produced in higher yield and specific activity using peroxyacetic acid, rather than N‐chlorosuccinimide as oxidant (90% and 4,000 Ci/mmol versus 50% and 2000 Ci/mmol).
Synthesis of carbon‐11 labelled calcium channel antagonists
Authors: Holschbach M. , Roden W. , Hamkens W.
Published: October 2006

A useful synthetic approach to carbon‐11 labelled 1,4‐dihydropyridines is described. Carbon‐11 labelled calcium channel antagonists 11C‐Nifedipine, 11C‐Nisoldipine, 11C‐Nitrendipine and 11C‐CF3‐Nifedipine were synthesized by a modified Hantzsch method using protected carboxy functions. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the corresponding potassium salts and subsequent methylation with 11CH3I produced the labelled compounds in very good chemical and radiochemical yields (94%).
Preparation of 4‐phenylbutyric [2,3‐2H2]‐, [4,4‐2H2]‐, [2,3,4,4‐2H4]‐, and [2,2,3,3,4,4‐2H6]‐acids by use of crossed kolbe electrolysis as a key reaction
Authors: Tashiro Masashi , Tsuzuki Hirohisa , Goto Hideyuki , Ogasahara Shoji , Mataka Shuntaro
Published: October 2006

The four deuteriated 4‐phenylbutyric [2,3‐2H2]‐, [4,4‐2H2]‐, [2,3,4,4‐2H4]‐, and [2,2,3,3,4,4‐2H6]‐acids have been synthesized in high isotopic purity by utilizing crossed Kolbe electrolysis of methyl hydrogen [2H0]‐, [2,3‐2H2], and [2,3,3,3‐2H4]‐succinates and phenyl acetic [2H0] and [2H2]‐acids as a key reaction.
Synthesis of racemic, R‐ and S‐[1‐11C]‐β‐hydroxybutyric acid
Authors: Thorell Jan‐Olov , Stone‐Elander Sharon , König Wilfried A. , Halldin Christer , Widén Lennart
Published: October 2006

Racemic, R‐ and S‐β‐hydroxybutyric acid were labelled with 11C in the carboxylic position by a two‐step stereospecific synthesis starting with carrier‐added [11C]cyanide and R/S, R‐ or S‐propylene oxide. Hydrolysis of the intermediate nitrile with hydrochloric acid gave racemic [1‐11C]‐β‐hydroxybutyric acid and R‐ or S‐[1‐11C]‐β‐hydroxybutyric acid with an enantiomeric excess of 87–97%. The total synthesis time (including HPLC puritication) was 45–50 min from end of trapping. The isolated decay‐corrected radiochemical yield was 20–30% based on [11C]cyanide. The radiochemical purity of the products was > 99%
Radiosynthesis of [11C]‐N‐methylacyclovir
Authors: Wilson Alan A. , Conti Peter S. , Dannals Robert F. , Ravert Hayden T. , Wagner Henry N.
Published: October 2006

A selective and potent analogue of the anti‐herpes agent acyclovir has been labelled with 11C in good yield and at high specific activities. 1‐[11C]‐Methyl‐9‐(2‐hydroxyethoxy)methyl)guanine may be useful for detecting HSV encephalitis using positron emission tomography.
An improved synthesis of [15N] labelled acetamide and acetonitrile
Authors: Morgan D. R. , Dorn H. C.
Published: October 2006

An improved synthesis of [15N] labelled acetamide and acetonitrile is described which provides these compounds in yields of 85% and 64%, respectively. The key difference in the present preparation is the use of 2,2,2‐trifluoroethyl acetate for the reaction with 15NH4OH.
Determination of the stereochemistry of tritium label in sulbactam obtained by isotope exchange of penicillanic acid (R)‐sulphoxide benzyl ester
Authors: Gibson Colin L. , Jones John R. , Sharratt Andrew P. , Liss Robert H.
Published: October 2006

Sulbactam, a β‐lactamase inhibitor, has been prepared in tritiated (170 mCi mmol−1) form by the highly stereospecific isotope exchange procedure involving penicillanic acid (R)‐sulphoxide benzyl ester. The stereochemistry of the tritiation has been established by 3H n.m.r. in conjunction with a 1H NOESY spectrum of sulbactam.
Preparation of the α‐[D]galvinoxyl radical
Authors: Tsiao C. , Wild C. , Gu J. , Dorn H. C.
Published: October 2006

The stable galvinoxyl radical has been prepared with specific deuterium substitution at the methylene carbon bridge between the two aromatic rings. The corresponding EPR spectrum illustrates only the small residual hyperfine coupling with the aromatic ring hydrogens.
Bisphosphonic compounds. I. Preparation of 13C‐ and 14C‐labelled clodronate
Authors: Jouko Vepsäläinen , Heikki Nupponen , Esko Pohjala
Published: October 2006

Tetrakis(1‐methylethyl) (methylene‐13C)bisphosphonate was obtained from 13C‐methyliodide via the Michaelis‐Arbuzov reaction with tris(1‐methylethyl)phosphite followed by condensation with chlorophosphonic acid bis(1‐methylethyl)ester. Tetrakis(1‐methylethyl) (methylene‐14C)bisphosphonate was prepared from 14C‐dibromomethane via the Michaelis‐Arbuzov reaction with excess of tris(1‐methylethyl)phosphite. Both of these labelled tetraesters were chlorinated with NaOCl, hydrolysed with HCl and neutralized with NaOH similarly. The overall yield of 13C‐clodronate, (dichloromethyl one‐13C)bisphosphonic acid disodium salt tetrahydrate, was 71% with 99.5% isotopic and 99.8% chemical purity. The overall radiochemical yield of 14C‐clodronate was 9.8%.
Enzymatic synthesis of labelled geraniol
Authors: Heide Lutz
Published: October 2006

[1‐14C]Geraniol was conveniently prepared from [1‐14C]isopentenyl pyrophosphate and dimethylallyl pyrophosphate in 56% yield.
Synthesis of a bis(aminoethanethiol) ligand with an activated ester group for protein conjugation and 99mTc labeling
Authors: Eisenhut M. , Mißfeldt M. , Lehmann W. D. , Karas M.
Published: October 2006

The N‐hydroxysuccinimide (NHS) ester of the bis(aminoethanethiol) (BAT) ligand, 6‐(4″‐(4″‐carboxyphenoxy) butyl)‐2, 10‐dimercap‐to‐2, 10‐dimethyl‐4, 8‐diazaundecane, was synthesized by reacting 7‐ (4′‐bromobutyl) ‐3,3, 11, 11‐tetramethyl‐1, 2‐dithia‐5, 9‐diazacycloundecane with the sodium salt of 4‐hydroxybenzoic acid ethyl ester, followed by ester hydrolysis, reductive disulfide cleavage with dithiothreitol (DTT) and activation of the carboxyl group with NHS and dicyclohexylcarbodiimide (DCC). The resulting NHS‐BAT ester was conjugated to monoclonal antibodies at pH 8.5 with about 40% yield. 2–4 BAT ligands conjugated to the antibody did not change the binding characteristics significantly. Proof of the amount of covalent bound BAT ligands was attained by UV‐laser desorption/ionization (UV‐LD/I) mass spectrometry. Complexation with 99mTc was accomplished by using the tin‐reduction method. The labeling efficiency was >90%.
Synthesis of a labelled terpene synthon, useful in the preparation of metabolites of Δ1‐tetrahydrocannabinol
Authors: Szirmai Maria , Halldin Magnus M , Ohlsson Agneta
Published: October 2006

The synthesis of an isotopically labelled terpene synthon (4) is described. The usefulness of this terpene synthon in the synthesis of Δ1‐THC metabolites is shown by preparation of (±)‐[2H10]‐Δ1‐THC‐7‐oic acid (5) by condensation of 4 with [2H7]‐olivetol. Compound 5 is suitable as internal standard for mass spectrometric assays.
Synthesis of (2‐methyl‐4‐nitro‐1‐[15N1]imidazolyl)acetic acid
Authors: Suwinski Jerzy , Szczepankiewicz Wojciech
Published: October 2006

1,4‐Dinitro‐2‐methylimidazole reacts under mild conditions with glycine to yield (2‐methyl‐4‐nitro‐1‐imidazolyl)acetic acid. The use of [15N]glycine gives a product having a labelled nitrogen in 1 position of 4‐nitroimidazole.
Solid phase synthesis of a tetrapeptide labelled with Carbon‐13. Preparation of L‐[U‐13C]lysyl‐L‐[1‐13C]arginyl‐L‐[3‐13C]asparyl‐L‐[1‐13C]serine
Authors: Humbert Thierry , Marsura Alain , Luu‐Duc Cuong
Published: October 2006

Synthesis of a [13C] tetrapeptide L‐[U‐13C]Lysyl‐L‐[1‐13C]Arginyl‐L‐[3‐13C]Aspartyl‐L‐[1‐13C] Serine (KRDS) on ap‐alkoxybenzyl ester polystyrene‐1% divinylbenzene resin support is described by using repetitive nonhydrolytic base cleavage of α‐amino protective groups in Solid Phase Peptide Synthesis (SPPS). Protected [13C] amino acid (AA) used in this SPPS model were prepared with 9‐Fluorenylmethyloxycarbonyl (Fmoc) protecting group and with different acid labile side chain protecting group over AA type as: Fmoc‐Ser(tert‐Bu)‐OH, Fmoc‐Asp(tert‐Bu)‐OH, Fmoc‐Arg(Pmc)‐OH and Fmoc‐Lys(Fmoc)‐OH. All the protected AA were coupled byN,N′‐dicyclohexyl carbodiimide (DCC) procedure, followed by Fmoc group cleavage using 20% piperidine inN,Ndimethylacetamide (DMA). Quantitative deblocking side‐chain AA protection and removal of KRDS from the solid support was effected by treatment with 50% trifluoroacetic acid in methylene chloride in a one pot‐procedure. Homogeneous free [13C] KRDS was obtained in 90% overall yield after HPLC purification. This synthesis schedule offered the advantage over present solid phase method which used acidolysis for repetitive α‐amino group deblocking.
Use of a microwave cavity to reduce reaction times in radiolabelling with [11C]cyanide
Authors: Thorell Jan‐Olov , Stone‐Elander Sharon , Elander Nils
Published: October 2006

Advantages of using a microwave cavity over thermal treatment are demonstrated for radiolabelling reactions with [11C]cyanide. For comparison purposes, two literature syntheses involving typical cyanide chemistry at rather vigorous conditions were investigated: cyano‐de‐halogenation with subsequent hydrolysis of the nitrile and the Bücher‐Strecker synthesis of an aromatic amino acid. Comparable yields were obtained with intensities < 100 W in reaction times that were 1/15 to 1/20th those used in thermal methods. Even rates of slower nucleophilic substitutions could be increased by manipulating the polarity of the medium. For the short‐lived radionuclide carbon‐11, such time gains result in radioactivity gains at the end‐of‐synthesis on the order of 70‐100%.
Synthesis of 14C and 3H labelled 6‐nitro‐7‐sulfamoylbenzo[f]quinoxalin‐2,3‐dione
Authors: Foged Christian , Jacobsen Poul
Published: October 2006

A 14C labelled form of 6‐nitro‐7‐sulfamoylbenzo[f]quinoxalin‐2,3‐dione [1] was synthesized in two steps from 1,2‐diamino‐5‐sulfamoylnaphthalene [2] and 30 mCi 14C‐oxalic acid. A total of 5.5 mCi was isolated as a yellow solid with a radiochemical purity > 99%. The specific activity was 99 mCi/mmol.

A 3H labelled form of [1] was synthesized in two steps from 10‐bromo‐7‐sulfamoylbenzo‐[f]quinoxalin‐2,3‐dione [4] and tritium gas. The product was isolated with a radiochemical purity of >98% and a specific activity of 10 Ci/mmol.
Preparation of multi‐labelled urocanic acids with 2H, 13C and 15N
Authors: Furuta Takashi , Katayama Motofusa , Shibasaki Hiromi , Kasuya Yasuji
Published: October 2006

Two types of multi‐labelled urocanic acids with stable isotopes, i.e., [3‐2H,1′,3′‐15N2]urocanic acid and [2,3,5′‐2H3,2′‐13C,1′,3′‐15N2]urocanic acid were synthesized by the enzymatic reaction of DL‐[3,3‐2H2,1′,3′‐15N2]histidine or DL‐[2,3,3,5′‐2H4,2′‐13C,1′,3′‐15N2]histidine with histidine ammonia‐lyase (Pseudomonas fluorescens) at pH 9.0. The reaction of DL‐[2,3,3,5′‐2H4,2′‐13C,1′,3′‐15N2]histidine was achieved in D2O buffer system (pD 9.0) to avoid the enzyme‐catalyzed hydrogen exchange at C‐5′ of the imidazole ring. The isotopic purities were demonstrated to be 94 atom%, based upon the ion intensities in the region of the molecular ions of respective gas chromatographic derivatives measured by GC‐MS.
Tritium labelling of two highly selective agonists for CCK‐B receptor: [3H]propionyl‐Tyr(SO3Na)‐gNle‐mGly‐Trp‐(N‐Me)Nle‐Asp‐Phe‐NH2([3H]pBC 264) [3H]propionyl‐γDLys‐Trp‐Nle‐Asp‐Phe‐NH2([3H]pBC 254)
Authors: Corringer P. J. , Durieux C. , Ruiz‐Gayo M. , Roques B. P.
Published: October 2006

Among the CCK‐B receptor agonists reported to date, the two modified peptides BC 264 and BC 254 display a high affinity and selectivity for this binding site and are highly protected from enzymatic degradation. Recently, we reported the biological properties of a tritiated analog of this agonist, [3H]pBC 264, which fullfils all the criteria required for in vitro as well as in vivo studies of the CCK‐B receptor. On the other hand, BC 254 displays a high affinity for the CCK‐B binding sites in the guinea‐pig (K1= 0.56 nM) while its affinity in the rat is more than 60‐fold lower, a difference which could be due to the occurrence of CCK‐B receptor subtypes. In the present paper, we report the synthesis of [3H]pBC 264 and of the new tritiated ligand [3H]pBC 254 using [3H] NPS (N‐succinimidyl[2,3‐3H]propionate) as labelling agent. These two probes have high specific activity (70–100 Ci/mmol) and will enable extensive studies of the CCK‐B receptors to be carried out.
The synthesis of 1,3,4‐thiadiazol‐2‐ylcyanamide sodium, a potentially useful anti‐influenza agent and its [5‐14C] and [UL‐13C3] isotopomers
Authors: Wheeler William J. , Blanchard William B.
Published: October 2006

As an aid to the study of the metabolism and disposition of LY217896 in laboratory animals and humans, 14C‐labeled material was prepared utilizing formic‐[14C] acid as the starting material. Uniformly labeled LY217896‐[13C] was also synthesized for use in metabolite identification. Formic acid, cyanogen bromide, and potassium cyanide which were >99% isotopically enriched with 13C were utilized; once the appropriate starting materials were synthesized, the synthesis of the 13C and 14C‐labeled materials were parallel.
Synthesis of carbon‐14 and tritium labeled analogs of Manoalide
Authors: Senderoff S. G. , Shu A. Y. L. , Lawrie K. , Heys J. R.
Published: October 2006

Several Manoalide analogs, 4‐(1‐acetyloxyalkyl)‐5‐hydroxy‐2(5H)‐furanones labeled with carbon‐14 in the alkyl side chain, were synthesized. The key step in these syntheses was singlet oxygenation of 2‐trialkylsilyl‐4‐alkylfurans to give the corresponding 4‐alkyl‐5‐hydroxy‐2(5H)‐furanones. The carbon‐14 label in the side chain was introduced earlier in the synthesis by reaction of the desired labeled alkyl Grignard reagent with the appropriate 2‐trialkylsilyl‐4‐furancarboxaldehyde and trapping of the resulting magnesium alkoxide with acetic anhydride. Labeled n‐alkyl Grignard reagents were obtained by carbonation of the corresponding nor‐alkyl bromides using ultrapure magnesium metal and barium carbonate‐ 14C followed by reduction of the resulting acid to the alcohol. Bromination followed by metallation gave the desired reagents. Manoalide analogs bearing a carbon‐14 or tritium label in the acetyl moiety of the side chain were synthesized by acetylation of the desired sidechain alcohol with acetyl chloride‐1‐ 14C, and by acetylation of the desired alcohol with dibromoacetic acid‐DCC followed by catalytic halogen‐tritium exchange and completion of the synthesis.
Biosynthetic preparation of the tritium labelled 3α‐hydroxy‐5α‐pregnan‐20‐one, an allosteric modulator of gabaergic neurotransmission
Authors: Jussofie Astrid , Jussofie Ibrahim , Stoppok Martin , Lax E. Rodney
Published: October 2006

A procedure for the biosynthetic preparation of 3α‐hydroxy‐5α‐[1,2,6,7‐3H]‐pregnan‐20‐one (3H‐HPO) with high specific activity convenient for binding studies was developed. 3H‐HPO was synthesized from [1,2,6,7‐3H]progesterone using a microsomal preparation from rat liver and NADPH. The progesterone metabolite was purified by silica gel 60 and Sephadex LH 20 chromatography. The identity of the product was confirmed by reverse isotopic dilution of chemically synthesized and highly purified 3α‐hydroxy‐5α‐pregnan‐20‐one. The yield for radiolabelled HPO was 60% and its purity was > 98%.
Understanding the mechanism of sweet taste: Synthesis of tritium labeled guanidineacetic acids
Authors: Nagarajan Srinivasan , Kellogg Michael S. , Dubois Grant E. , Williams David S. , Gresk Christopher J. , Markos Charles S.
Published: October 2006

Syntheses of tritium labeled guanidineacetic acid sweetener and a tritiated photoaffinty labeling reagent via the catalytic hydrogenation of the dibromo intermediates are described. These labeled compounds were required for the investigation of sweet taste mechanism.
A simple procedure for producing oxygen‐labelled inorganic phosphate from isotopically labelled water that optimizes yield based on the isotope
Authors: Ray William J.
Published: October 2006

Phosphorus pentachloride can be treated with stoichiometric amounts of oxygen‐labelled water to produce 80–90 percent yields of labelled inorganic phosphate when the reaction is conducted in dioxane. Any phosphorus‐chlorine bonds remaining at the end of the reaction are eliminated by reaction with diethylamine prior to adding water.
Preparation of di‐(2‐ethylhexyl) adipate and some of its metabolites labelled with deuterium
Authors: Moore Richard B
Published: October 2006

The syntheses of deutero‐labelled di‐(2‐ethylhexyl)adipate (DEHA), mono‐(2‐ethylhexyl) adipate (MEHA), 2‐ethylhexan‐1‐ol, 2‐ethylhexanoic acid, 2‐ethyl‐5‐ketohexanoic acid, 3‐ethyl‐6‐methyltetrahydro‐2H‐pyran‐2‐one and 2‐ethylhexanedioic acid are described. All compounds were perdeutero‐labelled in the ethyl group. The title compound, DEHA, was used in a human dosing study.
Synthesis of 2‐chloroethyl (13C)‐methyl sulfide
Authors: Taber Douglass F. , Meagley Robert P.
Published: October 2006

Incorporation of a stable isotope‐labelled methylthio group into the mustard 2‐chloroethyl methyl sulfide 2 was complicated by concomitant reaction with iodide ion, a necessary byproduct from the precursor stable isotope‐labelled iodomethane. A two step procedure was therefore employed, initial displacement with mercaptoethanol 4 being followed by chlorination with thionyl chloride.
Synthesis of 3‐[18F]‐fluoromethyl‐TCP1, A potential tool for pet study of the nmda receptor channel complex
Authors: Ponchant M. , Kamenkaj M. , Crouzel C.
Published: October 2006

In an attempt to visualize the NMDA glutamatergic receptors and after checking the biological activity of the cold 3‐fluoromethyl‐TCP 3, 3‐[18F]‐fluoro‐methyl‐TCP 4 was synthesized by a nucleophilic substitution of 3‐bromomethyl‐TCP 5 with [18F−].
Synthesis of [3H]tert‐butyl 8‐chloro‐5,6‐dihydro‐5‐methyl‐6‐oxo‐4h‐imidazo[1,5‐a][1,4]benzodiazepine 3‐carboxylate, a selective, high affinity ligand for the diazepam insensitive (DI) subtype of the benzodiazepine receptor
Authors: Gu Zi‐Qiang , de Costa Brian R. , Wong Garry , Rice Kenner C. , Skolnick Phil
Published: October 2006

The preparation of [3H]‐labelled tert‐butyl 8‐chloro‐5,6‐dihydro‐5‐methyl‐6‐oxo‐4H‐imidazo[1,5‐a][1,4]benzodiazepine 3‐carboxylate (TCIB, 6), a high affinity ligands for the diazepam insensitive (DI) subtype of the benzodiazepine receptor (BZR) is described. Synthesis of [3H]TCIB was accomplished in 4 steps starting from 5‐chloroisatoic anhydride. Tritium‐label introduction was achieved in the final step by selective catalytic tritiolysis in 62% radiochemical yield with quantitative isotopic incorporation.
Synthesis of [1′‐15N]‐biotin
Authors: Lee M.‐L. , Berger S.
Published: October 2006

Racemic [1′‐15N]‐biotin was synthesized from [15N]‐glycine as starting material in 7 steps. The overall yield was 13%.
Synthesis of radioiodinated 2′‐iodobutyrophenone derivatives
Authors: Nakatsuka Iwao , Shiba Kunio , Saji Hideo , Yoshitake Akira , Yokoyama Akira
Published: October 2006

To develop new radioligands labelled with radioiodine (125I, 131I and 121I) for in vitro and in vivo dopamine receptor studies, three iodinated butyrophenones (2′‐iodospiperone, 2′‐iodotrifluperidol and 2′‐iodohaloperidol) were designed, synthesized and labelled with 125I.
Synthesis of 14C‐labeled eschenmoser's salt: Dimethyl([14C]methylene)ammonium iodide
Authors: Kupczyk‐Subotkowska Lidia , Shine Henry J.
Published: October 2006

A six step synthesis of dimethyl([14C]methylene)ammonium iodide (Eschenmoser's salt) is described. Sodium [2‐14C]acetate was used as the starting material. The overall yield of the final product was 30% with specific activity 8 mCi/mol.
123I‐iodobenzoylglucosamines: Glucose analogues for heart imaging
Authors: Lutz T. , Dougan H. , Rihela T. , Vo C. V. , Lyster D. M.
Published: October 2006

The ortho‐, meta‐ and para‐[123I]‐2‐deoxy‐2‐N‐(iodobenzoyl)‐D‐glucosamine (BGA) derivatives were investigated to determine the effect of iodine position and lipophilicity on tissue distribution. There was no correlation between tissue uptake and lipophilicity. Maximum uptake was observed for o‐BGA displaying a heart:blood ratio of 36.0 at 18 hours post injection. Yeast hexokinase phosphorylation studies in vitro and an in vivo insulin experiment were carried out on o‐BGA. No phosphorylation was detected, but the insulin study indicated that o‐BGA uses the glucose transporter. o‐BGA showed maximum tissue uptake in mice at an optimal specific activity of 0.004mg/μCi. Mouse biodistribution studies of o‐[123I]‐iodobenzamide(o‐123IBA) indicated that the glucose moiety of o‐BGA may be involved in the heart accumulation process in mice. Heart tissue extraction studies showed unmetabolized o‐[123I]BGA, recorded at 14 hours post injection, showed significant heart uptake.
Preparation of α–[3‐11C]aminoisobutyric acid from an azadisilolidine derivative of alanine
Authors: Oberdorfer Franz , Zobeley Axel , Weber Klaus , Prenant Christian , Haberkorn Uwe , Maier‐Borst Wolfgang
Published: October 2006

Alkylation of ethyl 2‐(2,2,5,5‐tetramethyl‐[1,2,5,]azadisilolidine‐1‐yl)propionate with [11C]CH3I afforded, following acid hydrolysis and chromatographic purification, the non‐physiological α‐[3‐11C]aminoisobutyric acid within 40 min in yields of 5 ‐ 15% (not corrected for decay) related to initially produced [11C]CH3I. Usually 1.2·109 Bq of the tracer molecule were prepared for use in amino acid transport studies. Dilution with a known amount of unlabelled α‐aminoisobutyric acid (10 μmol) provided a constant specific radioactivity of 1.2·108 Bq·μmol−1 for each application. The radiochemical purity of that product was better than 98%, whereas the final carrier‐added solution typically contained 10 ‐ 45 μmol of alanine.
Introduction of tritium into organic compounds by isotope exchange reactions
Authors: Myasoedov N. F.
Published: October 2006

Various isotope exchange reactions for the introduction of tritium into a range of organic compounds have been investigated. The influence of the catalyst, solvent and reaction conditions on the yield and specific activities of a number of steroids, phytohormones and sugars are reported. Heterogeneous hydrogen isotope exchange with gaseous tritium has also been used to label a number of nonpolar compounds. Similarly the potential of solid state hydrogen isotope exchange has been explored. The reaction mechanism is discussed as well as the influence of the reaction conditions on the specific activity and the label distribution.
The synthesis of 5′‐[14C1] and 3a, 4‐[13C2] labelled panadiplon (U‐78875; 3‐(5′‐cyclopropyl‐1,2,4‐oxadiazol‐3‐yl)‐5‐(1‐methylethyl)‐imidazo‐[1,5a]‐quinoxalin‐4(5H)‐one).
Authors: Ackland M. J. , Howard M. R. , Dring L. G.
Published: October 2006

5′‐[14C1]Panadiplon was prepared in 3 steps starting from [14C1]cyclopropane carboxylic acid and 3‐(5′‐cyano‐1,2,4‐oxadiazol‐3‐yl)‐5‐(1‐methylethyl)‐imidazo‐[1,5a]‐quinoxalin‐4(5H)‐one. 3a, 4‐[13C2]Panadiplon was prepared in two steps from 13C2‐oxalic acid and N‐1‐(1‐methylethyl)‐o‐phenylenediamine. The position of labelling was confirmed by the appearance of two coupled resonances (JC‐C=80.59 Hz) at 121.95 and 154.39 ppm in the assigned 13C‐NMR spectrum.
Radiosynthesis of 1‐[11C] polyhomoallylic fatty acids
Authors: Channing Michael A. , Simpson Norman
Published: October 2006

A facile retro‐synthesis involving the radical chain decarboxylation of the N‐hydroxypyridine‐2‐thione esters of both arachidonic and docosahexaenoic acid was utilized to synthesize (all Z)‐1‐bromononadeca‐4,7,10,13‐tetraene, and (all Z)‐1‐bromoheneicosa‐3,6,9,12,15,18‐hexaene in 60% overall yield. The corresponding polyhomoallylic magnesium bromides were carbonated with [11C]CO2 to afford the 1‐[11C]polyhomoallylic labeled fatty acids in good yield in less than 35 minutes. The final radiochemical purities were found to be in excess of 95% by radio‐HPLC.
A rapid method for the synthesis of 5‐iodo‐2′‐ deoxyuridine (IUDR) and optimisation of the parameters
Authors: Trivedi Mahendra A.
Published: October 2006

A modified method for the synthesis of radioiodinated 5‐iodo‐2′‐deoxyuridine based on electrophillic iodination using concentrated HNO3 as an oxidising agent is described. It is easy, quick, reproducible and yields consistently high (>95%) radiolabelled IUDR. This method avoids refluxing at high temperatures, thereby saving preparation time and improving safety.
(αS, Z, 1R, 3R)‐[4′,4″‐3H]cyhalothrin and ‐[4″,6′,‐3H]4″‐fluorocyhalothrin: Synthesis of candidate pyrethroid radioligands for the sodium channel
Authors: Latli Bachir , Greenfield Laura J. , Casida John E.
Published: October 2006

(αS,Z,1R,3R)‐Cyhalothrin (1) and (αS,Z,1R,3R)‐4′‐fluorocyhalothrin (2), highly potent insecticides, were selected as candidate radioligands for studies on pyrethroid‐sodium channel interactions. This report describes the synthesis of dihalo derivatives of 1 and 2 and their reductive dehalogenation to the corresponding deuterium‐ and tritium‐labelled pyrethroids. Thus, reduction of 4″,6′‐dibromo‐2 with deuterium gas, platinum oxide and potassium carbonate in ethyl acetate went quantitatively to [4″,6′‐2H]‐2; however, the use of tritium instead of deuterium failed to yield [4″, 6′‐3H]‐2 giving instead decomposed materials. Fortunately the use of the iodo compounds 4″,4′‐diiodo‐1 and 4″,6′‐diiodo‐2 with tritium gas and palladium on carbon in absolute ethanol gave [4″,4′‐3H]‐1 and [4″,6′‐3H]‐2 in near quantitative yields at 55 Ci/mmol.
Synthesis of [3H]proadifen for studying binding to liver membranes
Authors: Werner Tom , Gawell Lars , Ross Svante B.
Published: October 2006

Tritium‐labelled proadifen (1, SKF 525A, 2‐(N,N‐diethylamino)‐ethyl‐2,2‐di‐diphenylpentanoate hydrochloride), a potent inhibitor of microsomal drug metabolism in the liver, was synthesized by hydrogenation of the corresponding allylic derivative with tritium gas. The specific activity of the compound obtained was 65 Ci/mmol. [3H]Proadifen was found to bind to washed rat liver membranes with high affinity (KD 1.3 nM) and large capacity Bmax 1300 pmol/g wet weight tissue.
Synthesis of the serotonin ligands, RS‐56532‐14C and RS‐66331‐14C from a common labelled intermediate
Authors: Masjedizadeh Mohammad R. , Parnes Howard
Published: October 2006

Two approaches towards the synthesis of 3‐chloro‐4‐amino‐1,8‐naphthalic anhydride‐[14C], which served as the common intermediate in the preparation of the two title compounds, are described. Although nucleophilic incorporation of the label via KCN was superior to an electrophilic sequence using CO2, the latter approach was adopted since the nitrile could not be hydrolyzed to the desired acid. The specific activities of RS‐56532‐14C and RS‐66331‐14C were 56.8 mCi/mmol and 53.7 mCi/mmol, respectively.
Synthesis and use of 4‐hydroxyphenyl derivatized phosphoramidites in the selective radioiodination of oligonucleotide probes
Authors: Fontanel M. L. , Bazin H. , Roget A. , Téoule R.
Published: October 2006

Synthetic oligonucleotides probes are nowadays readily available and widely used in the identification of specific gene sequence from bacteria, viruses, in the diagnostic of human genetic diseases as well as in the development of antisense therapy. Much effort has been devoted to the development of non radioactive probes, nevertheless the radioactive labelling is still extensively used for research purposes. In this study we propose a new and simple synthesis of 4‐hydroxyphenyl‐oligonucleotide conjugates which upon reaction with 125I give rise to radiolabelled probes. We describe two types of phosphoramidite reagents which allow the selective incorporation of a 4‐hydroxyphenyl group at a specific site of an oligonucleotide in the course of its chemical synthesis. The radioiodination step is fast and specific of the hydroxyphenyl group and shows a high incorporation yield.
Synthesis of tritium labeled 1‐amidino‐3‐(P‐nitro‐phenyl)urea: A potential antimalarial agent
Authors: Wang Theodore S. T. , Fawwaz Rashid A. , van Heertum Ronald L.
Published: October 2006

Five steps were required to synthesize the title compound. This involved a catalytic exchange reaction, nitration, hydrolysis, and condensation. The overall radiochemical yield was 28.87% and the specific activity was 12.4 mCi/mmol, with a radiochemical purity of more than 95.7%.
Synthesis of [20,21‐13C2]‐pregnenolone
Authors: Caballero Gerardo M. , Gros Eduardo G.
Published: October 2006

The synthesis of [20,21‐13C2]‐pregnenolone (7) from androst‐5‐en‐3β‐ol‐17‐one (1) is described. Labelled carbons were introduced by two procedures, namely, condensation of 1 with K13CN and Grignard reaction of nitrile derivative 5 with [13C]‐methylmagnesium iodide. Location of labels was confirmed by 13C‐NMR spectroscopy.
Synthesis of the β‐D‐glucosyl ester of [carbonyl‐13C]‐indole‐3‐acetic acid
Authors: Jakas Andreja , Magnus Volker , Horvat Stefica , Sandberg Göran
Published: October 2006

An efficient, operationally simple synthetic approach to 1‐O‐([carbonyl‐13C]‐indole‐3′‐ylacetyl)‐β‐D‐glucopyranose is described. The synthesis was carried out by fusing a fully benzylated 1‐O‐glucosylpseudourea intermediate with [carbonyl‐13C]‐indole‐3‐acetic acid, followed by hydrogenolytic removal of the protective groups.
Preparation of benzyl‐α‐D1‐alcohol by the reduction of benzaldehyde with raney alloys in an alkaline deuterium oxide solution
Authors: Tsukinoki Takehito , Ishimoto Keiko , Tsuzuki Hirohisa , Mataka Shuntaro , Tashiro Masashi
Published: October 2006

Benzyl‐α‐d1‐alcohol was prepared in high isotopic purity by the reduction of benzaldehyde with Raney Cu‐Al alloy in 10% Na2CO3‐D2O solution using ultrasonic irradiation.
Synthesis of 2E, 4E, 8E ‐ nonatetraenoic acid‐3, 7‐dimethyl‐1‐[14C]‐9‐(2′, 6′, 6′‐trimethylcyclohex‐1‐enyl)‐4‐(N‐acetamino) phenylester
Authors: Haynes Ute J. , Swigor J. E.
Published: October 2006

The title compound 4‐(N‐acetylamino) phenyl‐1‐[14C] retinoate (3) was synthesized by a 2‐step sequence. Carboxyl‐[14C] vitamin A (1) was treated with ethylchloroformate to form the mixed anhydride (2). Treatment with acetamidophenol and heating with a catalytical amount of 4‐dimethylaminopyridine produced 4‐(N‐acetylamino)phenyl‐1‐[14C] retinoate (3) with a specific activity of 23.4 μCi/mg and a radiochemical purity of 97.2% in an overall yield of 42%.
Synthesis and in vivo evaluation of a new fluorine‐18 labeled dopamine D2 radioligand synthesis with benzofuran benzamide skeleton
Authors: Takao Futoshi , Sasaki Shigeki , Maeda Minoru , Fukumura Toshimitsu , Tahara Takashi , Masuda Kouji , Ichiya Yuichi
Published: October 2006

N‐[(1‐Ethyl‐2‐pyrrolidinyl)methyl]‐5‐(2‐[18F]fluoroethyl)‐2,3‐dihydroben‐zofuran‐7‐carboxamide ([18F]5) was synthesized via nucleophilic substitution with K18F/Kryptofix222 complex in 5.4∼6.8% radiochemical yields with a specific activity of larger than 5.6 TBq/mmol (150 Ci/mmol) at the end of the 110 minutes synthetic period. Its in vivo affinity toward CNS dopamine D2 receptors was investigated using rats in order to evaluate as a radiotracer for the PET (positron emission tomography) study of the dopamine D2 receptors. In biodistribution experiments, [18F]5 exhibited striatal accumulation, although the whole brain radioactivity was cleared rapidly. The striatal/cerebellar radioactivity ratio, which corresponds to the ratio of a brain D2 receptor‐rich to poor region, gradually increased to about 12 at 60 minutes after the injection. The striatal uptake was inhibited with pretreated haloperidol, a dopamine D2 antagonist, indicating that the striatal accumulation was due to the specific binding with D2 receptors. Thus, [18F]5 appears to be a potential in vivo radiotracer for dopamine D2 receptors.
[2′‐18F]‐2‐oxoquazepam: Synthesis of a 5‐(2‐[18F]fluorophenyl)‐1,4‐benzodiazepine‐2‐one
Authors: Johnströma Peter , Stone‐Elander Sharon , Duelfer Tim
Published: October 2006

The use of a 2‐amino‐2′‐[18F]fluorobenzhydrol as a radiolabelling intermediate in the synthesis of a 1,4‐benzodiazepine‐2‐one is demonstrated. 5‐Chloro‐2′‐[18F]fluoro‐2‐(N‐(2,2,2‐trifluoroethyl)amino)benzhydrol, 2, was synthesized by the coupling of the anilinodichloroborane reagent with 2‐[18F]fluorobenzaldehyde, 1 and was subsequently oxidized to the benzophenone, 3, using Jones reagent in 70–80% conversions after 10 min at 0–5°C. After solid phase extraction, 3 reacted with bromoacetyl bromide to generate the bromoamide, 4, in 90–95% conversions after 10 min at 140°C. Ring closure of 4 to the 1,4‐benzodiazepine‐2‐one, 5, was accomplished using hexamethylenetetramine in aqueous dimethylsulfoxide. Conversions of 80–90% were obtained after 10 min at 100°C. Following preliminary cleaning by solid phase extraction, 5 was isolated by radio‐HPLC. The total time of synthesis was 180–190 min and the isolated yield was on the order of 107ndash;12% (decay‐corrected) or 3–4% (not decay‐corrected) and based on [18F]F−. The radiochemical purity of the isolated 1,4‐benzodiazepine‐2‐one was >99% and the specific activity was ∼2000 Ci/mmol at the end‐of‐synthesis.
Synthesis of carbon‐14 labelled cis‐malonato [(4R,5R)‐4,5‐bis(aminomethyl)‐2‐isopropyl‐1,3‐dioxolane] platinum(II) (ski 2053R)
Authors: Kim Dae‐Kee , Kim Youngseok , Rim Jonggill , Kim Ganghyeok , Gam Jongsik , Song Sungkun , Yoo Kwanghee , Kim Key H.
Published: October 2006

The synthesis of 14C‐labelled cis‐malonato[(4R,5R)‐4,5‐bis(aminomethyl)‐2‐isopropyl‐1,3‐dioxolane]platinum(II) from [1,4‐14C] D‐tartaric acid is described. The overall radiochemical yield of the product in a eight‐step sequence was 23.8% and radiochemical purity was 98.5%.
The synthesis of 6,6,6‐2H3‐2E‐hexenal
Authors: Fielder Simon , Rowan Daryl D.
Published: October 2006

6,6,6‐2H3‐2E‐Hexenal, leaf‐aldehyde, has been synthesized in 45% yield and 99.3% purity by reaction of 3,3,3‐2H3‐n‐propyl magnesium bromide with an ethereal solution of 3‐trimethylsiloxy‐2‐propenal (3) prepared in situ. This new one pot procedure alleviates the need to isolate (3) and should prove useful in the synthesis of other E‐α,β‐unsaturated aldehydes.
Synthesis of N‐{N‐[4‐(4‐{N‐[11C]methylamino}phenyl)butyryl]‐L‐prolyl}pyrrolidine: A potential radiotracer for prolyl endopeptidase
Authors: Van Dort Marcian E. , Kilbourn Michael R. , Mangner Thomas J.
Published: October 2006

The synthesis of the 4‐[11 C]methylamino derivative of N‐{N‐[4‐(4‐Aminophenyl)butyryl]‐L‐prolyl}pyrrolidine (SUAM‐1221), is described as a potential marker for prolyl endopeptidase for in vivo positron emission tomography studies. Direct methylation of the 4‐amino derivative of SUAM‐1221 (1) with methyl iodide provided a mixture of the 4‐monomethyl (2) and 4‐dimethylamino (3) derivatives which were separated by chromatography. Methylation of 1 with [11 C]methyl iodide provided the 4‐[11C]methylamino derivative of SUAM‐1221, ([11C]2), in 18–30% decay corrected radiochemical yield after HPLC purification, with a specific activity > 1700 Ci/mmol and a 40 minute synthesis time from end of bombardment.
A convenient synthesis of [3‐3H]squalene and [3‐3H]‐2,3‐oxidosqualene
Authors: Ceruti Maurizio , Grosa Giorgio , Rocco Flavio , Dosio Franco , Cattel Luigi
Published: October 2006

[3‐3H]Squalene and [3‐3H]‐2,3‐oxidosqualene, key compounds for studying the biosynthesis of sterols, were synthesized. The main step was a modified Wittig reaction of [1‐3H]trisnorsqualene aldehyde with a phosphorus ylide to give [3‐3H]squalene or with a sulfur ylide to give [3‐3H]‐2,3‐oxidosqualene. These compounds were obtained in high radiochemical yield and high purity under simple conditions.
Synthesis of [2‐14C,5‐3H]cytosine and [2‐14C,5‐3H]uracil via bromination and catalytic bromine‐tritium gas exchange
Authors: Asano Takeyoshi , Kiritani Reiko
Published: October 2006

In micro‐scale experiments, [2‐14C,5‐3H]cytosine and [2‐14C,5‐3H] uracil were synthesized via bromination and catalytic Br‐3H exchange reaction with the use of [2‐14C]‐cytosine and‐uracil and tritium gas. The double labelling percentages of these products were 70 and 26, respectively. It was assumed that [2‐14C,5‐Br] uracil was subjected to reaction with hydrogen atom originally adsorbed on a palladium catalyst. This is to a lesser extent valid for [2‐14C,5‐Br]cytosine. The percentages of 3H labelling at 5 position of pyrimidine ring of cytosine and uracil were proved to be 96 and 73, respectively. For the analysis and purification of products, the HPLC eluting conditions using C18 reverse column and NaH2PO4 aqueous solution or H2O/methanol mixture as eluent were studied. Unreacted tritium gas was recovered with the use of adsorbents such as active charcoal and Zr‐V‐Fe getter.
Preparation of carbon‐14 labeled 3,4‐dihydro‐5‐methyl‐1(2H)‐isoquinolinone
Authors: Ekhato I. Victor , Huang Che C.
Published: October 2006

Carbon‐14 labeled 3,5‐dihydro‐5‐methyl‐1(2H)‐isoquinolinone, a potent inhibitor of poly(ADP‐ribose) polymerase (ADPRP) was prepared from 1‐bromo‐2‐methylbenzene in 7.8 % overall yield. The C‐14 label was introduced from Ba14CO3 via metal‐halogen exchange and carboxylation reactions. Subsequent transformations yielded a propenecarbonyl azide 8 which was rearranged by Curtius reaction to the isocyanate, and a cyclization produced 5‐methyl‐1(2H)‐[4‐14C]isoquinolinone (9). From the compound 9 by Pd/C catalyzed hydrogenation 3,4‐dihydro‐5‐methyl‐1(2H)‐[4‐14C]isoquinolinone (10) was made.
The synthesis of 4‐(4‐([11C]methoxyphenyl) ‐(5‐fluoro‐2‐hydro‐xyphenyl)‐methylene‐aminobutyric acid, as a potential radioli‐gand for the gaba receptor in the brain
Authors: Vos Filip De , Slegers Guido
Published: October 2006

A procedure for the synthesis of 4‐(4‐[11C]methoxyphenyl) ‐(5‐fluoro‐2‐hydroxyphenyl)‐methylene‐aminobutyric acid has been developed. The production entailed a O‐methylation of 5‐fluoro‐2‐hydroxy‐4′‐hydroxybenzophenone with cyclotron produced [11C]iodomethane in the presence of alkali and a subsequent Schiff reaction of 5‐fluoro‐2‐hydroxy‐4′‐(11C]methoxybenzophenone with γ‐aminobutyric acid. 5‐Fluoro‐2‐hydroxy‐4′‐hydroxybenzophenone was obtained by a demethylation of the 4′‐methoxyderivative with boron tribromide. Subsequent purification by HPLC and sterilisation by filtration gave 740 MBq (20 mCi) of an injectable solution. The radiochemical yield (decaycorrected) from [11C]iodomethane achieved 27%. The specific activity was 3.7 GBq/μmol (100 mCi/μmol) at the end of the radiosynthesis (45 min from EOB). The preparations have been demonstrated to be chemically and radiochemically pure by HPLC and TLC.
Synthesis of isotopically‐labelled nitroxyl radicals for use as spin probes
Authors: Bolton Roger , Sutcliffe Leslie H. , Wu Xiaoping
Published: October 2006

The synthesis of [15N]‐1,1,3,3‐tetrakis(trideuteriomethyl)isoindolin‐2‐yloxyl and of some 5‐alkyl derivatives have been achieved by standard synthetic routes.1 The presence of deuterium improves the sharpness of the signals, and this, together with the incorporation of nitrogen‐15, enhances the application of such compounds as spin probes; alkyl substituents at C‐5 improve the lipophilicity.
An efficient synthesis of Nω‐[18F]fluoroacetylserotonin (Nω‐[18F]fluoroacetyl‐5‐hydroxytryptamine)
Authors: Tada Masao , Iwata Ren , Sugiyama Hiroshi , Sato Kazunori , Fukuda Hiroshi , Kubota Kazuo , Kubota Roko , Fujiwara Takehiko , Takahashi Hiromu , Wakui Akira , Ido Tatsuo
Published: October 2006

A rapid synthesis of Nω‐[18F]fluoroacetylserotonin (Nω‐[18F]fluoroacetyl‐5‐hydroxytryptamine) starting from [18F]fluoride and ethyl p‐toluensulfonyloxyacetate is described. The total time required for its synthesis is ca. 90 min. The radiochemical yield, purity, and specific activity (end of bombardment) of the desired hormone are 13.5%, >98%, and 600 mCi/μmol, respectively.
Tc‐99m markierte Östradiol‐derivate synthese, organverteilung und tumor‐affinität
Authors: Wenzel M. , Klinge C.
Published: October 2006

As starting material for the Tc‐99m labelling 17‐(Ferrocenyl‐ethinyl)‐estradiol and 16‐(Ferrocenyliden)‐estron were synthesized.

These ferrocene derivatives were heated with Mn‐Br(CO)5 and Tc‐99m‐pertechentate to yield the labelled corresponding cytectrene steroid compounds. In organ distribution studies with infantile female rats a binding of the Tc‐99m labelled steroids to the estradiol receptor in the rat uterus was demonstrated. The binding to MXT‐mamma tumors in mice yielded a Tc‐99m concentration ratio tumor/muscle of 3:1.
Synthesis of nitric oxide releasing, vasodilating and platelet aggregation inhibiting S‐[15N]nitroso compounds
Authors: Tsikas Dimitrios , Stichtenoth Dirk O. , Böger Rainer H. , Bode‐Böger Stefanie M. , Frölich Jürgen C.
Published: October 2006

[15N]Nitric oxide (15NO) was produced in a “gas‐tight” flask from [15N]nitrite by reaction with iodide in acetic acid acidified water and purged for 60 min by a continuous nitrogen gas stream applied through an uncoated polytetrafluoroethylene flate membrane into a second flask which contained a methanolic solution of N‐acetyl‐L‐cysteine or N‐acetyl‐DL‐penicillamine. Analysis of these solutions by UV spectroscopy, reversed‐phase high‐performance liquid chromatography and capillary isotachophoresis showed formation of the corresponding S‐nitroso compounds. Gas chromatographic‐mass spectrometric analysis for [15N]nitrite which was formed by dissolving these compounds in aqueous buffered solutions gave an isotopic purity higher than 95% at 15N. The S‐nitroso compounds were shown to inhibit ADP‐induced platelet aggregation.
Synthesis of radioactive and stable isotope labeled tirilazad mesylate
Authors: Stolle W. T. , Easter J. A. , Chew E. H. , McGrath J. P. , Palmer J. R. , Hsi R. S. P.
Published: October 2006

Tirilazad mesylate, 21‐[4‐(2,6‐di‐1‐pyrrolidinyl‐4‐pyrimidinyl)‐1‐piperazinyl]‐16α‐methyl‐pregna‐1,4,9(11)‐triene‐3,20‐dione monomethanesulfonate, is a potent lipid peroxidation inhibitor capable of suppressing progression of tissue damage caused by trauma or ischemia. Several isotopically labeled versions of the compound have been synthesized for conducting in vitro and in vivo metabolic transformations of this experimental drug. These include labeling with carbon‐14 at the 16α‐methyl group of the steroid portion of the molecule, or at the C‐2 position of the pyrimidine ring; also with deuterium at the steroid 16α‐methyl group, and/or with carbon‐13 at C‐2, C‐4, and C‐6, and with nitrogen‐15 at N‐1 and N‐3 of the pyrimidine ring.
Phosphinic acid analogues of γ‐aminobutyric acid (GABA). Synthesis of a new radioligand
Authors: Hall Roger G. , Kane Peter D. , Bittiger Helmut , Froestl Wolfgang
Published: October 2006

The synthesis of a new radioligand, which binds with high selectivity and affinity (KD = 7.4 nM) to the GABA‐B receptor, is described. A Wittig‐Horner approach was employed to prepare an unsaturated protected intermediate (6), suitable for tritiation and deprotection.
Application of solid state catalytic hydrogen isotope exchange to the tritium labeling of lysozyme
Authors: Filikov Anton V. , Jones John R. , Myasoedov Nikolai F. , Ward E. Sally
Published: October 2006

Solid state catalytic hydrogen isotope exchange has been employed to label hen egg lysozyme with tritium. Optimization of reaction conditions so that amino acids and peptide bonds remained intact led to a tritiated product with 97% of the original enzymatic activity and 94% radiochemical purity. The specific activity when using a T2:H2 mixture of 1:1000, was 16 mCi·mmol−1. It is suggested that the currently adopted approach may have wide applications for other proteins able to tolerate lyophilization conditions without loss of activity.
Synthesis of [76Br]4‐bromodexetimide and [76Br]4‐bromolevetimide: Radiotracers for studying muscarinic cholinergic receptors using PET
Authors: Kassiou Michael , Loc'h Christian , Strijckmans Veronique , Katsifis Andrew , Lambrecht Richard M. , Maziere Mariannick , Maziere Bernard
Published: October 2006

The muscarinic cholinergic receptor antagonist dexetimide and its pharmacologically inactive enantiomer levetimide were labelled with the positron emitter bromine‐76. [76Br]4‐Bromodexetide, [76Br]BrDEX, and [76Br]4‐bromolevetimide, [76]BrLEV, were prepared via electrophilic bromodesilylation of 4‐(trimethylsilyl)dexetimide and 4‐(trimethyylsilyl)levetimide with [76Br]NH4. The use of chloramine‐T in acid media resulted in radiochemical yields of 80%. The radiotracers were purified by semi‐preparative reverse‐phase HPLC. Radiochemical and chemical purities were assessed by radio‐TLC and HPLC and found to be 98%. The average time of synthesis including formulation was 60 minutes resulting in average specific activities of 300 mCi/μmol.
Synthese d'une serie de calix[8]arenes marques au carbone 14
Authors: Montagne‐Marcellin C. , Archimbaud M. , Ansoborlo E. , Cristau H. J.
Published: October 2006

This paper describes syntheses of paratertiobutyl calix[8]arene, calix[8]arene, and parasulfonic calix[8]arene acid, labelled with 14C on the methylene position. Parasulfonic calix[8]arene acid when injected to rats, allowed to know the hydrosoluble calixarenes distribution in organism. Initial labelled reactant is Amersham formaldehyde. 1H.NMR spectra of each compound and assembly of the first two syntheses are described.
[123I]iodomethane, a main product in the synthesis of 5‐[123I]iodo‐6‐nitroquipazine by iododestannylation
Authors: Zea‐Ponce Yolanda , Baldwin Ronald M. , Miliust Richard A. , Bakthavachalam Venkatesalu , Innis Robert B.
Published: October 2006

Radioiodinated 5‐iodo‐6‐nitroquipazine (2‐piperazinyl‐5‐iodo‐6‐nitroquinoline), a selective serotonin transporter radiotracer, can be prepared by the reaction of its N‐t‐BOC‐5‐trimethylstannyl precursor with [125I] or [123I]NaI in the presence of chloramine‐T, followed by amine deprotection by heating under acidic conditions. However, the labeling reaction is associated with a large and consistent formation of a volatile radioactive reaction product [37 ± 4% (n = 11] for 123I and 40 ± 4% (n = 3) for 125I).

The purpose of these experiments was to characterize the volatile radioactive product and to examine the effect of reaction temperature on its formation. The volatile radioactive product was identified as [125I] or [123I]iodomethane by its trapping characteristics and by its retention time in two different HPLC systems. Changing the reaction temperature (22–124°C) did not have a significant effect in the amount of labeled iodomethane produced (n = 13).

The conditions chosen for the radioiodination and deprotection were: 50 μg precursor in MeOH, dry Na123I, 50 μl 0.02 M chloramine‐T in glacial HOAc/MeOH, heating at 90°C for 15 min, followed by deprotection with CF3CO2H for 5‐10 min at the same temperature. Purification was achieved by solvent extraction and HPLC.

Radiochemical yields for preparations carried out at temperatures between 86°C and 124°C were 24 ± 5% (n = 11) for [123I]‐ and 45 ± 13% (n = 3) for 5‐[125I]iodo‐6‐nitroquipazine; radiochemical purity averaged 95 ± 4% and 99 ± 0% respectively.
Synthesis of carbon‐11 labeled methylcarbamates from [11C]‐methylchloroformate
Authors: Ravert Hayden T. , Mathews William B. , Musachio John L. , Dannals Robert F.
Published: October 2006

[11C]‐Methylchloroformate, a novel [11C]‐acylating agent, was generated in situ from [11C]‐methanol and phosgene. To explore the utility of [11C]‐methylchloroformate, this agent was reacted with several amines to yield their corresponding [11C]‐labeled methylcarbamates. The average synthesis (including purification and formulation) required approximately 23 minutes from end of bombardment. The average specific activity was calculated to be approx. 607 mCi/μmole at end of synthesis with an average radiochemical yield of 6%, decay corrected to starting [11C]‐methanol. Preliminary results reveal that [11C]‐methylchloroformate is a useful general reagent for the preparation of [11C]‐methyl carbamates of both primary and secondary amines.