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Decay-corrected Radiochemical Yield (decay-corrected + radiochemical_yield)
Selected AbstractsHighly 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 [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] 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 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 [1- 11C]ethyl iodide from [11C]carbon monoxide and its application in alkylation reactionsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 11 2004Jonas Eriksson Abstract A method is presented for preparing [1- 11C]ethyl iodide from [11C]carbon monoxide. The method utilizes methyl iodide and [11C]carbon monoxide in a palladium-mediated carbonylation reaction to form a mixture of [1- 11C]acetic acid and [1- 11C]methyl acetate. The acetates are reduced to [1- 11C]ethanol and subsequently converted to [1- 11C]ethyl iodide. The synthesis time was 20 min and the decay-corrected radiochemical yield of [1- 11C]ethyl iodide was 55 ± 5%. The position of the label was confirmed by 13C-labelling and 13C-NMR analysis. [1- 11C]Ethyl iodide was used in two model reactions, an O -alkylation and an N -alkylation. Starting with approximately 2.5 GBq of [11C]carbon monoxide, the isolated decay-corrected radiochemical yields for the ester and the amine derivatives were 45 ± 0.5% and 25 ± 2%, respectively, based on [11C]carbon monoxide. Starting with 10 GBq of [11C]carbon monoxide, 0.55 GBq of the labelled ester was isolated within 40 min with a specific radioactivity of 36 GBq/µmol. Copyright © 2004 John Wiley & Sons, Ltd. [source] Substitution-reduction: an alternative process for the [18F]N -(2-fluoroethylation) of anilinesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 4 2004Emmanuelle Briard Abstract Substitution of a halo atom (chloro or bromo) in easily prepared N -haloacetyl-anilines with no-carrier added (NCA) cyclotron-produced [18F]fluoride ion (18F, t1/2= 109.8 min; ,+=96.9%), followed by reduction with borane,tetrahydrofuran (BH3,THF), provides an alternative route to NCA [18F]N -(2-fluoroethyl)-anilines. This two-step and one-pot process is rapid (,50 min) and moderately high yielding (,40% decay-corrected radiochemical yield (RCY) overall). In the nucleophilic substitution reaction, 18-crown-6 is preferred to Kryptofix® 222 as complexing agent for the solubilization of the counter-ion (K+), derived from an added metal salt, in acetonitrile. Weakly basic potassium bicarbonate is preferred as the added metal salt. Inclusion of a small amount of water, equating to 4,5 molar equivalents relative to 18-crown-6, base or precursor (held in equimolar ratio), is beneficial in preventing the adsorption of radioactivity onto the wall of the glass reaction vessel and for achieving high RCY in the nucleophilic substitution reaction. BH3,THF is effective for the rapid reduction of the generated [18F]N -fluoroacetyl-aniline to the [18F]N -(2-fluoroethyl)-aniline. Copyright © 2004 John Wiley & Sons, Ltd. [source] Preparation of 4-[11C]methylmetaraminol, a potential PET tracer for assessment of myocardial sympathetic innervationJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 1 2003Oliver Langer Abstract The false adrenergic neurotransmitter [11C]meta -hydroxyephedrine ([11C]HED) is currently the PET tracer of choice for assessment of myocardial sympathetic innervation. The molecule is metabolised in the 4-position of the aromatic ring. The resulting radiolabelled metabolites need to be measured in order to obtain an arterial input function. Our aim was the development of a PET tracer with an increased metabolic stability relative to [11C]HED. We selected 4-methylmetaraminol as a candidate molecule for radiolabelling with 11C (t1/2 20.4 min). Our radiosynthetic approach towards 4-[11C]methylmetaraminol involved a palladium-catalyzed cross-coupling reaction of a protected 4-trimethylstannyl derivative of metaraminol with [11C]methyl iodide followed by removal of the protective groups. 4-[11C]methylmetaraminol was obtained in a final decay-corrected radiochemical yield of 20,25% within a synthesis time of 60,80 min. The specific radioactivity at the end of the synthesis ranged from 18,37 to GBq/,mol. The unlabelled reference molecule, 4-methylmetaraminol, was prepared in a 5-step synthesis starting from metaraminol. A biological evaluation of 4-[11C]methylmetaraminol is in progress and the results will be reported elsewhere. Copyright © 2002 John Wiley & Sons, Ltd. [source] Synthesis of (±) 3-(6-nitro-2-quinolinyl)-[9-methyl- 11C]-3,9-diazabicyclo-[4.2.1]-nonane ([11C-methyl]NS 4194)JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2002Svend B. Jensen Abstract (±) 3-(6-Nitro-2-quinolinyl)-[9-methyl- 11C]-3,9-diazabicyclo-[4.2.1]-nonane ([11C-methyl]NS 4194), a selective serotonin reuptake inhibitor (SSRI), was synthesised within 35 min after end of bombardment with a radiochemical purity >98%. It had a decay-corrected radiochemical yield of 7% after preparative HPLC, and a specific radioactivity around 37 GBq/,mol (EOS). A typical production starting with 40 GBq [11C]CO2 yielded 800 MBq of radiolabelled [11C-methyl]NS 4194 in a formulated solution. The synthesis of the precursor to [11C-methyl]NS 4194, (±) 9-H-3-[6-nitro-(2-quinolinyl)]-3,9-diazabicyclo-[4.2.1]-nonane, as well as the unlabelled analogue (±) 9-methyl 3-[6-nitro-(2-quinolinyl)]-3,9-diazabicyclo-[4.2.1]-nonane (NS 4194), are also described. Copyright © 2002 John Wiley & Sons, Ltd. [source] Synthesis of [1- 11C]ethyl iodide from [11C]carbon monoxide and its application in alkylation reactionsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 11 2004Jonas Eriksson Abstract A method is presented for preparing [1- 11C]ethyl iodide from [11C]carbon monoxide. The method utilizes methyl iodide and [11C]carbon monoxide in a palladium-mediated carbonylation reaction to form a mixture of [1- 11C]acetic acid and [1- 11C]methyl acetate. The acetates are reduced to [1- 11C]ethanol and subsequently converted to [1- 11C]ethyl iodide. The synthesis time was 20 min and the decay-corrected radiochemical yield of [1- 11C]ethyl iodide was 55 ± 5%. The position of the label was confirmed by 13C-labelling and 13C-NMR analysis. [1- 11C]Ethyl iodide was used in two model reactions, an O -alkylation and an N -alkylation. Starting with approximately 2.5 GBq of [11C]carbon monoxide, the isolated decay-corrected radiochemical yields for the ester and the amine derivatives were 45 ± 0.5% and 25 ± 2%, respectively, based on [11C]carbon monoxide. Starting with 10 GBq of [11C]carbon monoxide, 0.55 GBq of the labelled ester was isolated within 40 min with a specific radioactivity of 36 GBq/µmol. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||