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Radiochemical Yield (radiochemical + yield)
Kinds of Radiochemical Yield Selected AbstractsPalladium-Mediated 11C-Carbonylative Cross-Coupling of Alkyl/Aryl Iodides with Organostannanes: An Efficient Synthesis of Unsymmetrical Alkyl/Aryl [11C- carbonyl]KetonesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2005Farhad Karimi Abstract [11C]Carbon monoxide in low concentration, palladium complexes, alkyl/aryl iodides, and organostannanes are utilized in the synthesis of twenty alkyl [carbonyl- 11C]ketones. The activated palladium(0) species [Pd{P(o -Tol)3}2] was generated in situ from tris(dibenzylideneacetone)palladium(0) [Pd2(dba)3] and a large excess of tri- o -tolylphosphane [P(o -Tol)3]. The Stille coupling reactions were performed in a micro-autoclave system. Radiochemical yields of 11C-labelled alkyl/aryl ketones were in the range of 37,98,% with specific radioactivity up to 300 GBq,,mol,1. Using this method, 4'-aminoacetophen[13C- arbonyl)one 6 was synthesised in order to confirm the position of labelling (, = 196.7 ppm, CDCl3). The presented approach is an efficient way for synthesising 11C-labelled alkyl/aryl ketones with acceptable radiochemical yield and is generally applicable in 13C-labelling syntheses. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Synthesis and characterization of 4,6-dichloroindole-based radioligands for imaging the glycine site of the NMDA ion channelJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2002R. N. Waterhouse Abstract To provide effective PET or SPECT ligands for the glycine binding site of the NMDA ion channel, we have synthesized and characterized in vitro four substituted derivatives of the potent glycine site antagonist 3-[2-[(phenylamino)carbonyl]ethenyl]-4,6-dichloroindole-2-carboxylic acid (Ki=3.0 nM). These new ligands contain groups amenable to labeling with C-11 for PET, or I-123 for SPECT. In vitro analysis of these compounds revealed that placement of a methoxy group at either the ortho or para position of the phenylaminocarbonyl group significantly reduced receptor affinity (Ki=74.0±8.1 and 26.5±4.9 nM, respectively), as did placement of an iodine at the para position (Ki=60.4±8.2 nM). However, the meta -methoxy derivative (4b) maintained high affinity (Ki=4.8±0.9 nM) for the glycine site and was therefore labeled with carbon-11 by reacting the corresponding desmethyl derivative with [11C]methyl iodide. Radiochemical yields of 14±10% (EOS), and high specific activity (1.2±0.5 Ci/,mol (EOS, n=7)) were realized, and the product was prepared in a sterile saline solution suitable for in vivo use. Copyright © 2002 John Wiley & Sons, Ltd. [source] Palladium-Mediated 11C-Carbonylative Cross-Coupling of Alkyl/Aryl Iodides with Organostannanes: An Efficient Synthesis of Unsymmetrical Alkyl/Aryl [11C- carbonyl]KetonesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2005Farhad Karimi Abstract [11C]Carbon monoxide in low concentration, palladium complexes, alkyl/aryl iodides, and organostannanes are utilized in the synthesis of twenty alkyl [carbonyl- 11C]ketones. The activated palladium(0) species [Pd{P(o -Tol)3}2] was generated in situ from tris(dibenzylideneacetone)palladium(0) [Pd2(dba)3] and a large excess of tri- o -tolylphosphane [P(o -Tol)3]. The Stille coupling reactions were performed in a micro-autoclave system. Radiochemical yields of 11C-labelled alkyl/aryl ketones were in the range of 37,98,% with specific radioactivity up to 300 GBq,,mol,1. Using this method, 4'-aminoacetophen[13C- arbonyl)one 6 was synthesised in order to confirm the position of labelling (, = 196.7 ppm, CDCl3). The presented approach is an efficient way for synthesising 11C-labelled alkyl/aryl ketones with acceptable radiochemical yield and is generally applicable in 13C-labelling syntheses. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Highly Enantioselective Synthesis of No-Carrier-Added 6-[18F]Fluoro- L -dopa by Chiral Phase-Transfer AlkylationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 13 2004Christian Lemaire Abstract [18F]Fluoro- L -dopa, an important radiopharmaceutical for positron emission tomography (PET), has been synthesized using a phase-transfer alkylation reaction. A chiral quaternary ammonium salt derived from a Cinchona alkaloid served as phase-transfer catalyst for the enantioselective alkylation of a glycine derivative. The active methylene group of this Schiff-base substrate was deprotonated with cesium hydroxide and rapidly alkylated by the 2-[18F]fluoro-4,5-dimethoxybenzyl halide (X = Br, I). The reaction proceeded with high yield (> 90%) at 0 °C or room temperature in various solvents such as toluene or dichloromethane. Preparation of the [18F]alkylating agent on a solid support was developed. After labelling, the labeled [18F]fluoroveratraldehyde was trapped on a tC18 cartridge and then converted on the cartridge into the corresponding benzyl halide derivatives by addition of aqueous sodium borohydride and gaseous hydrobromic or -iodic acid. Hydrolysis and purification by preparative HPLC made 6-[18F]fluoro- L -dopa ready for human injection in a 25,30% decay-corrected radiochemical yield in a synthesis time of 100 min. The product was found to be chemically, radiochemically and enantiomerically pure (ee > 95%). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Synthesis and biological evaluation of a radioiodinated spiropiperidine ligand as a potential ,1 receptor imaging agentJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 9 2010Rui-Qin Chen Abstract We report the synthesis and evaluation of 1,-(4-[125I]iodobenzyl)-3H-spiro[isobenzofuran-1,4,-piperidine] ([125I]Spiro-I) as a potential SPECT tracer for imaging of ,1 receptors. [125I]Spiro-I was prepared in 55,65% isolated radiochemical yield, with radiochemical purity of >99%, via iododestannylation of the corresponding tributyltin precursor. In receptor binding studies, Spiro-I displayed low nanomolar affinity for ,1 receptors (,1: Ki=2.75±0.12,nM; ,2: Ki=340,nM) and high subtype selectivity (,2/,1=124). Biodistribution in mice demonstrated relatively high concentration of radioactivity in organs known to contain ,1 receptors, including the lung, kidney, heart, spleen, and brain. Administration of haloperidol 5,min prior to injection of [125I]Spiro-I significantly reduced the concentration of radioactivity in the above-mentioned organs. These findings suggest that the binding of [125I]Spiro-I to ,1 receptors in vivo is specific. Copyright © 2010 John Wiley & Sons, Ltd. [source] Radiosynthesis of 13N-labeled thalidomide using no-carrier-added [13N]NH3JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2010Katsushi Kumata Abstract Recent studies revealed that thalidomide (1) has unique and broad pharmacological effects on multi-targets although the application of 1 in therapy is still controversial. In this study, we synthesized nitrogen-13-labeled thalidomide ([13N]1) as a potential positron emission tomography (PET) probe using no-carrier-added [13N]NH3 as a labeling agent. By use of an automated system, [13N]1 was prepared by reacting N -phthaloylglutamic anhydride (2) with [13N]NH3, following by cyclization with carbonyldiimidazole in a radiochemical yield of 56±12% (based on [11N]NH3, corrected for decay) and specific activity of 49±24,GBq/µmol at the end of synthesis (EOS). At EOS, 570,780,MBq (n=7) of [13N]1 was obtained at a beam current of 15,µA after 15,min proton bombardment with a synthesis time of 14,min from the end of bombardment. Using a small animal PET scanner, preliminary biodistribution of [13N]1 in mice was examined. Copyright © 2010 John Wiley & Sons, Ltd. [source] Carbon-14 radiosynthesis of combretastatin A-1 (CA1) and its corresponding phosphate prodrug (CA1P)JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2009Rodney T. Brown Abstract The natural product combretastatin A-1 (CA1) is isolated from the African bush willow tree, a member of the Combretaceae family. CA1 has important medicinal value, due in part to its ability to inhibit tubulin assembly. The prodrug combretastatin A-1 diphosphate (CA1P; OXi4503) is currently in human Phase I clinical trials as a vascular disrupting agent. This paper describes the carbon-14 radiosynthesis of [4,- 14C]CA1 and the corresponding phosphate prodrug salt [4,- 14C]CA1P in high specific activity (55,mCi/mmol). The carbon-14 label was introduced by methylation of the C-4, protected phenolic moiety of the CA1 precursor following removal of the tert -butyldimethylsilyl protecting group in the presence of [14C]methyl iodide. This was accomplished in excellent yield without significant Z to E isomerization. The [14C]-precursor ((Z)-1-[3,,[4,- 14C],5,-trimethoxyphenyl]-2-[2,,3,-di-[(isopropyl)oxy]-4,-methoxyphenyl] ethene) was subjected to a de- isopropylation reaction with TiCl4. The tetrabenzyl phosphate derivative of the resulting diol was prepared using fresh dibenzyl phosphite. Debenzylation with trimethylsilylbromide, followed by hydrolysis of the trimethylsilyl ester and adjustment of the pH with dilute aqueous hydrochloric acid yielded [4,- 14C]CA1P with an overall radiochemical yield of 8.4%. Copyright © 2009 John Wiley & Sons, Ltd. [source] Synthesis and biological evaluation of [carboxyl - 11C]eprosartanJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2009Ola Åberg Abstract Essential hypertension occurs in approximately 25% of the adult population and one cause of hypertension is primary aldosteronism. Targeting the angiotensin II AT1 receptor using PET and an appropriate tracer may offer a diagnostic method for adrenocortical tissue. This report describes the synthesis of the selective AT1 receptor antagonist [carboxyl - 11C]eprosartan 10, 4-[2-butyl-5-((E)-2-carboxy-3-thiophen-2-yl-propenyl)-imidazol-1-ylmethyl]-[carboxyl - 11C]benzoic acid, and its precursor (E)-3-[2-butyl-3-(4-iodo-benzyl)-3H -imidazol-4-yl]-2-thiophen-2-ylmethyl-acrylic acid 9. 11C-carboxylation of the iodobenzyl moiety was performed using a palladium-mediated reaction with [11C]carbon monoxide in the presence of tetra- n -butyl-ammonium hydroxide in a micro-autoclave using a temperature gradient from 25 to 140°C over 5,min. After purification by semipreparative HPLC, [carboxyl - 11C]eprosartan 10 was obtained in 37,54% decay-corrected radiochemical yield (from [11C]carbon monoxide) with a radiochemical purity >95% within 35,min of the end of bombardment (EOB). A 5-µAh bombardment gave 2.04,GBq of 10 (50% rcy from [11C]carbon monoxide) with a specific activity of 160,GBq,µmol,1 at 34,min after EOB. Frozen-section autoradiography shows specific binding in kidney, lung and adrenal cortex. In vivo experiments in rats demonstrate a high accumulation in kidney, liver and intestinal wall. Copyright © 2009 John Wiley & Sons, Ltd. [source] Two-step radiosynthesis of [18F]N -succinimidyl-4-fluorobenzoate ([18F]SFB)JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2009Matthias Glaser Abstract The acylation reagent [18F]N -succinimidyl-4-fluorobenzoate (18F-SFB) has been prepared using a new two-step approach. The starting material p- [18F]fluorobenzaldehyde (18F-FBA) was obtained by an improved radiosynthesis with a decay-corrected radiochemical yield of 66±6 % (n=3). Reaction of 18F-FBA with (diacetoxyiodine)benzene and N -hydroxysuccinimide and preparative HPLC purification furnished 18F-SFB in an r.c.y. of 49±6 % (n=3), based on the starting radioactivity of 18F-FBA. The radiochemical purity of 18F-SFB was >99%. Alternatively, purification by solid phase extraction gave 18F-SFB with an r.c.y. of 77±9% (n=4) and a radiochemical purity of 89±5% (n=4). This radiochemical synthesis only used non-aqueous solvents, which simplifies the method and facilitates subsequent applications of 18F-SFB. Copyright © 2009 John Wiley & Sons, Ltd. [source] An investigation of the 125I-radioiodination of colchicine for medical purposesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 1 2009K. M. El-Azony Abstract A procedure for radioiodination of colchicine with iodine-125 is carried out via an electrophilic substitution reaction. The reaction parameters studied were colchicine concentration, pH of the reaction mixture, reaction time, temperature, different oxidizing agents and different organic media to optimize the conditions for the labeling of colchicine and to obtain a high radiochemical yield of the 125I-colchicine (125I-Col). Using 3.7,MBq of Na125I, 1.25,mM of colchicine as substrate, 1.1,mM of chloramine-T (CAT) as oxidizing agent in ethanol at 60°C for 5,min, a maximum radiochemical yield of 125I-Col (60%) was obtained. The specific activity of 125I-Col obtained was 44.4,MBq/0.5,mmol, and the labeled compound was not completely separated and purified from Col by means of high-pressure liquid chromatography (HPLC), so the uncertainty in the purity may affect the distribution and clearance routes due to the expected competition between 125I-Col and Col. The biological distribution in normal mice indicates the suitability of radioiodinated colchicine for imaging of muscles. Copyright © 2008 John Wiley & Sons, Ltd. [source] 18F-Labelled vorozole analogues as PET tracer for aromataseJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 5 2008Maria Erlandsson Abstract One- and two-step syntheses for the 18F-labelling of 6-[(S)-(4-chlorophenyl)(1H -1,2,4-triazol-1-yl)methyl]-1-(2-[18F]fluoroethyl)-1H -benzotriazole, [18F]FVOZ, 1 and 6-[(S)-(4-chlorophenyl)(1H -1,2,4-triazol-1-yl)methyl]-1-[2-(2-[18F]fluoroethoxy)ethyl]-1H -benzotriazole, [18F]FVOO, 2 were developed. In the two-step synthesis, the nucleophilic fluorination step was performed by reacting (S)-6-[(4-chlorophenyl)-(1H -1,2,4-triazol-1-yl)methyl]-1H -benzotriazole (VOZ) with either the 18F-labelled ethane-1,2-diyl bis(4-methylbenzenesulfonate) or the oxydiethane-2,1-diyl bis(4-methylbenzenesulfonate). The radiochemical yields were in the range of 9,13% after the 110,120,min total syntheses and the specific radioactivities were 175±7,GBq/µmol and 56,GBq/µmol for compounds 1 and 2, respectively. In the one-step synthesis, the precursor 2-{6-[(4-chlorophenyl)(1H -1,2,4-triazol-1-yl)methyl]-1H -1,2,3-benzotriazol-1-yl}ethyl 4-methylbenzenesulfonate (7) or 1-[2-(2-bromoethoxy)ethyl]-6-[(4-chlorophenyl)(1H -1,2,4-triazol-1-yl)methyl]-1H -benzotriazole (8) was directly labelled via an 18F nucleophilic substitution to give the corresponding tracer. The labelled compounds were obtained in 36,99% radiochemical yield after 75-min syntheses. The specific radioactivities are 100,GBq/µmol for compound 1 and 80,GBq/µmol for compound 2. In vitro autoradiography using frozen rat brains illustrated specific binding in the medial amygdala, the bed nucleus of stria terminalis and the preoptic area, all of which corresponded well to the result of 11C-labelled vorozole. Copyright © 2008 John Wiley & Sons, Ltd. [source] Radiosynthesis of novel 18F-labelled derivatives of indiplon as potential GABAA receptor imaging tracers for PETJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2008Steffen Fischer Abstract The involvement of gamma amino butyric acid (GABA) receptors in a variety of neurological and psychiatric diseases has promoted the development and use of radiolabelled benzodiazepines (BZ) for brain imaging by PET. However, these radioligands are unable to distinguish between the various subtypes of GABAA receptors. Novel non-BZ such as the pyrazolo-pyrimidine indiplon proved to be selective for the ,1 -subunit of the GABAA receptor. Here, we describe the syntheses of four novel 18F-labelled indiplon derivatives. Radiosyntheses were performed via n.c.a. 18F-nucleophilic substitution starting from the tosyl, bromo, and 4-nitrobenzoyl precursors to obtain fluorine substituted N -alkylamide side chain derivatives of indiplon, followed by multistep purification using semi-preparative high-performance liquid chromatography and solid phase extraction. Tosyl and bromo precursors were converted into 18F-labelled indiplon derivatives with good and reproducible radiochemical yield (RCY) (35,70%, decay corrected), high radiochemical purity (,98.5%), and high specific activity (,>,150,GBq/µmol). By contrast, a low RCY (5,10%) and specific activity (10,15,GBq/µmol) were achieved for the 4-nitrobenzoyl precursor. Copyright © 2008 John Wiley & Sons, Ltd. [source] Towards stereoselective radiosynthesis of ,-[11C]methyl-substituted aromatic ,-amino acids , a challenge of creation of quaternary asymmetric centre in a very short time,JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 5-6 2007Alexander Popkov Abstract In positron emission tomography (PET) , -methyl amino acids have two potential applications: As analogues of neutransmitter precursors for the study of neurodegenerative diseases; as non-metabolised analogues of proteinogenic amino acids for the study of amino acid uptake into normal and cancer cells. Clinical applications of such amino acids are strongly limited due to their poor availability. We carried out [11C]methylation of metalocomplex synthons derived from protected DOPA or tyrosine. For [11C]methylation, sodium hydroxide (5 mg of fine dry powder) was sealed in a vial, which was flushed with dry nitrogen before addition of a solution of the complex (10 mg) and 11CH3I in 1,3-dimethylimidazolidin-2-one (300 µl). After 10 min at 25°C, a 9% radiochemical yield (decay-corrected) of a mixture of the diastereomeric , -[11C]methylDOPA complexes or a 7% radiochemical yield of a mixture of the diastereomeric , -[11C]methyltyrosine complexes was achieved. Individual diastereomers were successfully separated by preparative HPLC, diluted with excess of water and extracted on C18 cartridges. Optimisation of the procedure including hydrolysis of the complexes (hydrolytic deprotection of enantiomerically pure amino acids) and subsequent purification of the enantiomers of , -[11C]methylDOPA and , -[11C]methyltyrosine is underway. Copyright © 2007 John Wiley & Sons, Ltd. [source] Preparation and in vitro evaluation of 99mTc-labelled bovine lactadherin as a novel radioligand for apoptosis detectionJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 4 2007Lasse N. Waehrens Abstract Lactadherin is an opsonin, which binds with high affinity to phosphatidylserine exposed on the surface of apoptotic cells via its C1C2 domains. Phagocytosis of the apoptotic cells is then facilitated by an Arg-Gly-Asp (RGD)- mediated binding to macrophages surface integrins. The present report describes the synthesis of 99mTc-HYNIC,lactadherin with a radiochemical yield of 88±5% (n= 3) and a specific activity of 41±5 µCi/µg (n=3) when purified. Purified 99mTc-HYNIC,lactadherin was shown to be stable for at least 5 h when supplemented with 1.5 mg/ml fatty-acid-free BSA. The radiolabelled protein retained its phospholipid binding ability that was verified by its ability to bind to apoptotic HL60 leukaemia cells. The apoptotic cells demonstrated a RGD independent 3- to 4-fold excess binding of the radioactive component relative to control cells. Surplus of unlabelled lactadherin almost completely inhibited the binding of 99mTc-HYNIC,lactadherin. Collectively our data indicate that 99mTc-HYNIC,lactadherin is potentially useful as a new molecular binding tool for the identification of apoptotic cells. Copyright © 2007 John Wiley & Sons, Ltd. [source] Simple and high radiochemical yield synthesis of 2,-Deoxy-2,-[18F]fluorouridine via a new nosylate precursorJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2006Se Hun Kang Abstract We synthesized 2'-deoxy-2'-[18F]fluorouridine (7) as a radiotracer for positron emission tomography from a new nosylate precursor (6). This new precursor was synthesized from uridine in four steps. The overall synthetic yield was 9.4% and we have high stability of >98% purity up to 6 months at 4°C. The optimal manual [18F]fluorination conditions were 30 mg of the precursor 6 in 500 µl of acetonitrile at 145°C for 15 min with 370 MBq of [18F]fluoride. The [18F]fluorination yield was 76.5±2.7% (n = 3). After hydrolysis of protecting groups with 1 N HCl and purification by HPLC, the overall radiochemical yield and purity were 26.5±1.4% and 98.2±2.5%, respectively. The preparation time was 70.0±10.5 min (n = 3 for each result). We also developed an automated method with a radiochemical yield and purity of 24.0±2.8 and 98.0±1.5% (n = 10) using a GE TracerLab MX chemistry module. This new nosylate precursor for 2'-deoxy-2'-[18F]fluorouridine synthesis showed higher radiochemical yields and reproducibility than previous methods. Copyright © 2006 John Wiley & Sons, Ltd. [source] Synthesis of 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazin-1-ylsulfonyl]-2- n -propoxyphenyl}-7- n -propyl-3,5-dihydro-4H -pyrrolo[3,2- d]-[2- 14C]pyrimidin-4-one·2 HCl (14C-SK3530·2 HCl)JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 13 2006Hyun-Il Shin Abstract A new 14C-labelled PDE5 inhibitor, 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazin-1-ylsulfonyl]-2- n -propoxyphenyl}-7- n -propyl-3,5-dihydro-4H -pyrrolo[3,2- d ]-[2- 14C]pyrimidin-4-one·2 HCl (14C-SK3530·2 HCl) (1·2 HCl) was synthesized through a straightforward six-step sequence from the readily available [14C-carbonyl]methyl salicylate (2). The overall radiochemical yield of the 1·2 HCl from 2 was 10.5%, and its radiochemical purity was 98.8%. Copyright © 2006 John Wiley & Sons, Ltd. [source] 4-[18F]fluorophenyl ureas via carbamate-4-nitrophenyl esters and 4-[18F]fluoroaniline,JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 12 2006Sebastian Olma Abstract Four different no carrier added (n.c.a.) 4-[18F]fluorophenylurea derivatives are synthesized as model compounds via two alternative routes. In both cases carbamate-4-nitrophenylesters are used as intermediates. Either n.c.a. 4-[18F]fluoroaniline reacts with carbamates of several amines, or the carbamate of n.c.a. 4-[18F]fluoroaniline is formed at first and an amine is added subsequently to yield the urea derivative. The choice of the appropriate way of reaction depends on the possibilities of precursor synthesis. The radiochemical yields reach up to 80% after 50 min of synthesis time while no radiochemical by-products can be determined. These high yields were possible due to an optimized preparation of n.c.a. 4-[18F]fluoroaniline with a radiochemical yield of up to 90%. From the various ways of its radiosynthesis, the substitution with n.c.a. [18F]fluoride on dinitrobenzene is chosen, using phosphorous acid and palladium black for reduction of the second nitro group. Copyright © 2006 John Wiley & Sons, Ltd. [source] Syntheses of [14C]BAY 59-7939 and its radiolabeled metabolite M-4JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 11 2006U. Pleiss Abstract BAY 59-7939 is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic diseases. Radiolabeled BAY 59-7939 was required for drug absorption, distribution, metabolism and excretion (ADME studies). The BAY 59-7939 was labeled with carbon-14 in the carboxamide group in one step in an overall radiochemical yield of 85% starting from 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}mor-pholin-3-one and 5-chlorothiophene-2-[14C]carboxylic acid. The radiolabeled metabolite M-4 was prepared in 77% yield starting from [1- 14C]glycine and 5-chlorothiophene-5-carboxylic acid. Copyright © 2006 John Wiley & Sons, Ltd. [source] Synthesis of 18F-labeled cyclooxygenase-2 (COX-2) inhibitor as a potential PET imaging agentJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 7 2006Haibin Tian Abstract A new PET tracer for COX-2 imaging, the 6-ethoxy-3-(4-methanesulfonylphenyl)-4-(4-[18F]fluorophenyl)pyran-2-one ([18F]EFMP), was synthesized. For F-18 radiolabeling, a trimethylammonium precursor and a brominated precursor were synthesized from 1,1,2,3-tetrachlorocycloprop-2-ene in 6 steps. The radiolabeling was achieved through nucleophilic substitution using no-carrier-added (n.c.a.) fluorine-18. Solid-phase extraction and semi-preparative-HPLC purification produced [18F]EFMP in 14.6±3.3% (n =4) decay corrected radiochemical yield with a specific activity of 487±85.1 (n =4) Ci/mmol and greater than 98% radiochemical purity. Copyright © 2006 John Wiley & Sons, Ltd. [source] Syntheses of [2H3, 15N], [14C]NexavarÔ and its labeled metabolitesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 7 2006U. Pleiss Abstract NexavarÔ, Sorafenib tosylate (BAY 43-9006 tosylate) is a potent small molecule Raf kinase inhibitor for the treatment of hyperproliferative disorders such as cancer. Both radiolabeled and stable isotope labeled compounds were required for drug absorption, distribution, metabolism and excretion (ADME) and quantitative mass spectrometry bio-analytical studies. NexavarÔ labeled with carbon-14 in the carboxamide group was prepared in two steps in an overall radiochemical yield of 42% starting from 4-chloro- N -methyl-2-pyridine-[14C]carboxamide. The [2H3,15N] version of NexavarÔ was prepared in 75% yield based on 4-chloro- N -[2H3]methyl-2-pyridine-[15N]carboxamide. The pyridine N -oxide metabolite labeled with carbon-14 as well as with deuterium and nitrogen-15 and was synthesized by oxidation in yields of 59% and 87%, respectively. Starting from [2H2, 13C]formaldehyde the N -hydroxymethyl metabolite was labeled with carbon-13 and deuterium in one step in a 45% overall yield. Copyright © 2006 John Wiley & Sons, Ltd. [source] Synthesis of [11C- carbonyl]hydroxyureas by a rhodium-mediated carbonylation reaction using [11C]carbon monoxideJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 5 2006Julien Barletta Abstract [11C]Hydroxyurea has been successfully labelled using [11C]carbon monoxide at low concentration. The decay-corrected radiochemical yield was 38±3%, and the trapping efficiency of [11C]carbon monoxide in the order of 90±5%. This synthesis was performed by a rhodium-mediated carbonylation reaction starting with azidotrimethylsilane and the rhodium complex being made in situ by chloro(1,5-cyclooctadiene)rhodium(I) dimer ([Rh(cod)Cl]2) and 1,2- bis(diphenylphosphino)ethane (dppe). (13C)Hydroxyurea was synthesized using this method and the position of the labelling was confirmed by 13C-NMR. In order to perform accurate LC,MS identification, the derivative 1-hydroxy-3-phenyl[11C]urea was synthesized in a 35±4% decay-corrected radiochemical yield. After 13 µA h bombardment and 21 min synthesis, 1.6 GBq of pure 1-hydroxy-3-phenyl[11C]urea was collected starting from 6.75 GBq of [11C]carbon monoxide and the specific radioactivity of this compound was in the order of 686 GBq/µmol (3.47 nmol total mass). [11C]Hydroxyurea could be used in conjunction with PET to evaluate the uptake of this anticancer agent into tumour tissue in individual patients. Copyright © 2006 John Wiley & Sons, Ltd. [source] Synthesis of N -(3-[18F]Fluoropropyl)-2, -carbomethoxy-3, -(4-iodophenyl)nortropane ([18F]FP- , -CIT)JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2006R. P. Klok Abstract N -(3-[18F]fluoropropyl)-2, -carbomethoxy-3, -(4-iodophenyl)nortropane ([18F]FP- , -CIT) was synthesized in a two-step reaction sequence. In the first reaction, 1-bromo-3-(nitrobenzene-4-sulfonyloxy)-propane was fluorinated with no-carrier-added fluorine-18. The resulting product, 1-bromo-3-[18F]-fluoropropane, was distilled into a cooled reaction vessel containing 2, -carbomethoxy-3, -(4-iodophenyl)-nortropane, diisopropylethylamine and potassium iodide. After 30 min, the reaction mixture was subjected to a preparative HPLC purification. The product, [18F]FP- , -CIT, was isolated from the HPLC eluent with solid-phase extraction and formulated to yield an isotonic, pyrogen-free and sterile solution of [18F]FP- , -CIT. The overall decay-corrected radiochemical yield was 25 ± 5%. Radiochemical purity was > 98% and the specific activity was 94 ± 50 GBq/µmol at the end of synthesis. Copyright © 2006 John Wiley & Sons, Ltd. [source] 18F-glycosylation using Koenigs,Knorr conditions: a comparative studyJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2006Simone Maschauer Abstract We compared two 18F-glycosylation methods, the BF3 -mediated 18F-glycosylation versus the newly developed AgOTf-activated 18F-glycosylation procedure. The AgOTf-activated 18F-glycosylation makes use of 3,4,6-tri-O-acetyl-2-deoxy-2-[18F]fluoro-glucopyranosyl bromide and revealed an improved radiochemical yield of 67±6% in the case of a protected serinyl precursor as compared to 27±4% obtained by the BF3 -method. This suggests the suitability of Koenigs,Knorr conditions for 18F-glycosylation of protected bioactive peptides. Copyright © 2006 John Wiley & Sons, Ltd. [source] Automated radiosynthesis of [18F]SPA-RQ for imaging human brain NK1 receptors with PETJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 1 2006Frederick T. Chin Abstract [18F]SPA-RQ is an effective radioligand for imaging brain neurokinin type-1 (NK1) receptors in clinical research and drug discovery with positron emission tomography. For the automated regular production of [18F]SPA-RQ for clinical use in the USA under an IND we chose to use a modified commercial synthesis module (TRACERlab FXF-N; GE Medical Systems) with an auxiliary custom-made robotic cooling,heating reactor, after evaluating several alternative radiosynthesis conditions. The automated radiosynthesis and its quality control are described here. [18F]SPA-RQ was regularly obtained within 150 min from the start of radiosynthesis in high radiochemical purity (>99%) and chemical purity and with an overall decay-corrected radiochemical yield of 15±2% (mean±S.D.; n=10) from cyclotron-produced [18F]fluoride ion. The specific radioactivity of [18F]SPA-RQ at the end of synthesis ranged from 644 to 2140 mCi/µmol (23.8,79.2 GBq/µmol). Copyright © 2005 John Wiley & Sons, Ltd. [source] Utility of 1,3,4,6-tetra- O -acetyl-2-deoxy-2-[18F]fluoro-glucopyranoside for no-carrier-added 18F-glycosylation of amino acidsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2005Simone Maschauer Abstract A radiochemical method for the 18F-glycosylation of amino acid side chains was developed starting from peracetylated 2-deoxy-2-[18F]fluoroglucopyranoside (TA-[18F]FDG). O -(2-deoxy-2-[18F]fluoro- D -glucopyranosyl)- L -serine and the corresponding threonyl compound were obtained in a radiochemical yield of 25% and 12% (related to [18F]fluoride), respectively, after Zemplén deprotection within a total reaction time of 90 min. The anomeric configuration of the corresponding 19F-substituted compounds revealed preferential , -stereoselectivity. The 18F-glycosylation method using TA-[18F]FDG is compatible with the short half-life of fluorine-18 and combines glycosylation and 18F-labelling of a target compound within a single reaction step. TA-[18F]FDG is a promising 18F-labelled prosthetic group and could be adapted to 18F-labelling of bioactive peptides to study their pharmacokinetics using positron emission tomography (PET). Copyright © 2005 John Wiley & Sons, Ltd. [source] Synthesis of (R)- and (S)-[O-methyl - 11C]N -[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]- N,-(4-methoxy-phenyl)-urea as candidate high affinity ,1 -adrenoceptor PET radioligandsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2005Stefan Wagner Abstract Molecular imaging and quantification of myocardial ,1 -adrenoceptor (AR) rather than total , -AR density is of great clinical interest since cardiac biopsy studies suggest that myocardial ,1 -AR density is reduced in patients with chronic heart failure whereas cardiac ,2 -AR density may vary. Positron emission tomography (PET), with appropriate radioligands, offers the possibility to assess , -AR density non-invasively in humans. However, no PET radioligand for the selective imaging of cardiac ,1 -ARs is clinically available. Here some derivatives of the well characterized ,1 -AR selective antagonist, ICI 89,406, namely the enantiomers of N -[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]- N,-(4-hydroxy-phenyl)-urea (5a and 5b) were synthesized and evaluated in vitro. The (R)-isomer 5a was more ,1 -selective but has lower affinity than its (S)-enantiomer 5b (,1 -AR selectivity: 6100 vs 1240; ,1 -affinity: K1 = 0.288 nM vs K1 = 0.067 nM). Etherification of the analogous desmethyl precursors, 5e and 5f, respectively, with [11C]iodomethane gave 11C-labelled versions of 5a and 5b, namely 5g and 5h, in 44 ± 5% radiochemical yield (decay-corrected) and 97.4 ± 1.3% radiochemical purity with specific radioactivities of 26.4 ± 9.4 GBq/µmol within 41.2 ± 3.4 min from the end of bombardment (n = 14). 5g and 5h are now being evaluated as candidate radioligands for myocardial ,1 -ARs. Copyright © 2005 John Wiley & Sons, Ltd. [source] Radiosynthesis and in vivo study of [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine: a promising new sigma-1 receptor ligandJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2005Jun Zhao Abstract The novel sigma-1 receptor PET radiotracer [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([18F]WLS1.002, [18F]-2) was synthesized (n=6) by heating the corresponding N -ethylmesylate precursor in an anhydrous acetonitrile solution containing [18F]fluoride, Kryptofix K222 and potassium carbonate for 15 min. Purification was accomplished by reverse-phase HPLC methods, providing [18F]-2 in 59±8% radiochemical yield (EOB), with specific activity of 2.89±0.80 Ci/µmol (EOS) and radiochemical purity of 98.3±2.1%. Rat biodistribution studies revealed relatively high uptake in many organs known to contain sigma-1 receptors, including the lungs, kidney, heart, spleen, and brain. Good clearance from normal tissues was observed over time. Blocking studies (60 min) demonstrated high (>80%) specific binding of [18F]-2 in the brain, with reduction also noted in other organs known to express these sites. Copyright © 2005 John Wiley & Sons, Ltd. [source] Synthesis of C-14-labeled novel IKK inhibitor: 2-[14C]- N -(6-chloro-9H-pyrido [3,4-b]indol-8-yl)-3-pyridinecarboxamideJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 5 2005Yuexian Li Abstract 2-[14C]- N -(6-Chloro-9H-pyrido [3,4-b]indol-8-yl)-3-pyridinecarboxamide (9A, also referred to as [14C]-PS-1145) was synthesized from [14C]-paraformaldehyde in five steps in an overall radiochemical yield of 15%. The key intermediate 1-[14C]-6-chloro-1,2,3,4-tetrahydro- , -carboline was obtained by Pictet,Spengler cyclization of chlorotryptamine with [14C]-paraformaldehyde. Similar reactions were conducted with tryptamine to address the generality of the methodology. Copyright © 2005 John Wiley & Sons, Ltd. [source] Synthesis of 6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline: a prospective irreversible EGFR binding probeJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2005Neil Vasdev Abstract Acrylamido-quinazolines substituted at the 6-position bind irreversibly to the intracellular ATP binding domain of the epidermal growth factor receptor (EGFR). A general route was developed for preparing 6-substituted-4-anilinoquinazolines from [18F]fluoroanilines for evaluation as EGFR targeting agents with PET. By a cyclization reaction, 2-[18F]fluoroaniline was reacted with N, -(2-cyano-4-nitrophenyl)- N,N -dimethylimidoformamide to produce 6-nitro-4-(2-[18F]fluoroanilino)quinazoline in 27.5% decay-corrected radiochemical yield. Acid mediated tin chloride reduction of the nitro group was achieved in 5 min (80% conversion) and subsequent acylation with acrylic acid gave 6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline in 8.5% decay-corrected radiochemical yield, from starting fluoride, in less than 2 h. Copyright © 2005 John Wiley & Sons, Ltd. [source] Synthesis of [quinoline-3- 14C]-SSR97193 (ferroquine) from [2- 14C]-malonic acidJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2004Alan McNeill Abstract The antimalarial [quinoline-3- 14C]-SSR97193 (ferroquine) (8), an analogue of chloroquine (CQ) (1), was synthesized from [2- 14C]-malonic acid with an overall radiochemical yield of 15%. The synthetic route via [14C]-Meldrum's acid (9) was designed to minimize the intermediacy of radiolabelled volatiles. This synthesis involves a four-step route to labelled 4,7-dichloroquinoline, which is the key intermediate for the synthesis of many analogues of CQ. Copyright © 2004 John Wiley & Sons, Ltd. 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