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PET Tracers (pet + tracer)
Selected Abstracts18F-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] 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] Efficient synthesis of [11C]befloxatone, a selective radioligand for the in vivo imaging of MAO-A density using PETJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 9 2003F. Dollé Abstract Carbon-11 labelled befloxatone ((5R)-5-(methoxymethyl)-3-[4-[(3R)-4,4,4-trifluoro-3-hydroxybutoxy]phenyl]-2-oxazolidinone) is a reversible and selective monoamine oxidase-A (MAO-A) inhibitor and appears to be a new potent PET tracer for the in vivo imaging of MAO-A density. In this paper, the radiosynthesis of befloxatone was investigated and orientated towards the preparation of multi milliCuries of radiotracer. Typically, using no-carrier-added [11C]phosgene, 150,300 mCi (5.55,11.10 GBq) of [11C]befloxatone was obtained within 20 min of radiosynthesis (including HPLC purification) with specific radioactivities ranging from 500 to 2000 mCi/µmol (18.5,74.0 GBq/µmol). The high efficiency of these radiosyntheses allows for multi-injection protocols and kinetic approaches for absolute quantification of the tracer. Copyright © 2003 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] Radiolabelling with short-lived PET (positron emission tomography) isotopes using microfluidic reactorsJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 3 2009Philip W Miller Abstract This mini-review covers the issues concerning the application of microfluidics towards radiolabelling with short-lived isotopes used for PET (positron emission tomography), and surveys the literature in this area. The application of microfluidic reactors to radiolabelling reactions is currently receiving a great deal of interest because of the potential advantages they have over conventional labelling systems. The volume and variety of radiolabelling reactions for PET is expected to grow markedly over the coming years due to increased demands for PET scanning. High demands and expectations for radiolabelled compounds will have to be met by exploiting new types of chemistry and technologies, such as microfluidics, to improve the production and development of PET tracers. Copyright © 2008 Society of Chemical Industry [source] HPLC methods for the purification of [11C]-labelled radiopharmaceuticals: reversal of the retention order of products and precursorsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 5 2009Szabolcs Lehel Abstract Preparative HPLC methods have been developed for a number of [11C]-methylated PET tracers, which enable elution of the labelled compounds prior to their precursors, thus reducing the overall synthesis time and avoiding contamination of the final product with precusor. This reversal of retention order has been achieved for [11C]DASB, [11C]raclopride, [11C]FLB 457, [11C]carfentanil, and 2-fluoro-[N -methyl- 11C]apomorphine, enabling collection of the purified radiopharmaceuticals from the HPLC system after 5,7,min. Furthermore, by using ethanol as the organic modifier, residual solvent analysis prior to human injection could be avoided and three of the radiopharmaceuticals could be injected directly following simple dilution and sterile filtration. Copyright © 2009 John Wiley & Sons, Ltd. [source] Synthesis of [N -methyl- 11C]mianserin: a tetracyclic, atypical antidepressantJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2001K. Marthi Abstract As part of our program to develop PET tracers for investigating monoaminergic processes in the brain, mianserin, a tetracyclic, atypical antidepressant, was selected as a candidate for labelling with 11C for in vivo evaluation. [N -methyl- 11C]Mianserin was produced by the alkylation of N -desmethyl mianserin with [11C]methyl iodide followed by HPLC purification and formulation. [N -methyl- 11C]Mianserin was obtained with a radiochemical purity >93% in a 16% decay corrected radiochemical yield. For a typical production starting with 40 GBq [11C]CO2, 1.9 GBq [N -methyl- 11C]mianserin was obtained as a formulated solution in a synthesis time of 35 min (counted from EOB). Copyright © 2001 John Wiley & Sons, Ltd. [source] Correlation of angiogenesis with 18F-FMT and 18F-FDG uptake in non-small cell lung cancerCANCER SCIENCE, Issue 4 2009Kyoichi Kaira L-[3- 18F]-,-methyltyrosine (18F-FMT) is an amino-acid tracer for positron-emission tomography (PET). We have conducted a clinicopathologic study to elucidate the correlation of angiogenesis with 18F-FMT and 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in patients with non-small cell lung cancer (NSCLC). Thirty-seven NSCLC patients were enrolled in this study, and two PET studies with 18F-FMT and 18F-FDG were performed. Uptake of PET tracers was evaluated with standardized uptake value. Vascular endothelial growth factor (VEGF), CD31, CD34, L-type amino acid transporter 1 (LAT1) and Ki-67 labeling index of the resected tumors were analyzed by immunohistochemical staining, and correlated with the clinicopathologic variables and the uptake of PET tracers. The median VEGF rate was 45% (range, 10,78%). High expression was seen in 30 patients (81%, 30/37). VEGF expression was statistically associated with progressively growing microvessel count. VEGF showed a correlation with LAT1 expression (P = 0.04) and Ki-67 labeling index (P = 0.01). However, it showed no correlation with age, gender, disease stage, tumor size, and histology. Microvessel density (MVD) showed no correlation with any parameters. 18F-FMT and 18F-FDG uptake correlated significantly with VEGF (P < 0.0001, P = 0.026, respectively), whereas the correlation of 18F-FMT and VEGF was more meaningful. The present study demonstrated that the metabolic activity of primary tumors as evaluated by PET study with 18F-FMT and 18F-FDG is related to tumor angiogenesis and the proliferative activity in NSCLC. (Cancer Sci 2009; 100: 753,758) [source] General Method for the 11C-Labeling of 2-Arylpropionic Acids and Their Esters: Construction of a PET Tracer Library for a Study of Biological Events Involved in COXs ExpressionCHEMISTRY - A EUROPEAN JOURNAL, Issue 14 2010Misato Takashima-Hirano Abstract Cyclooxygenase (COX) is a critical enzyme in prostaglandin biosynthesis that modulates a wide range of biological functions, such as pain, fever, and so on. To perform in vivo COX imaging by positron emission tomography (PET), we developed a method to incorporate 11C radionuclide into various 2-arylpropionic acids that have a common methylated structure, particularly among nonsteroidal anti-inflammatory drugs (NSAIDs). Thus, we developed a novel 11C-radiolabeling methodology based on rapid C -[11C]methylation by the reaction of [11C]CH3I with enolate intermediates generated from the corresponding esters under basic conditions. One-pot hydrolysis of the above [11C]methylation products also allows the synthesis of desired 11C-incorporated acids. We demonstrated the utility of this method in the syntheses of six PET tracers, [11C]Ibuprofen, [11C]Naproxen, [11C]Flurbiprofen, [11C]Fenoprofen, [11C]Ketoprofen, and [11C]Loxoprofen. Notably, we found that their methyl esters were particularly useful as proradiotracers for a study of neuroinflammation. The microPET studies of rats with lipopolysaccharide (LPS)-induced brain inflammation clearly showed that the radioactivity of PET tracers accumulated in the inflamed region. Among these PET tracers, the specificity of [11C]Ketoprofen methyl ester was demonstrated by a blocking study. Metabolite analysis in the rat brain revealed that the methyl esters were initially taken up in the brain and then underwent hydrolysis to form pharmacologically active forms of the corresponding acids. Thus, we succeeded in general 11C-labeling of 2-arylpropionic acids and their methyl esters as PET tracers of NSAIDs to construct a potentially useful PET tracer library for in vivo imaging of inflammation involved in COXs expression. [source] Pd0 -Mediated Rapid Coupling between Methyl Iodide and Heteroarylstannanes: An Efficient and General Method for the Incorporation of a Positron-Emitting 11C Radionuclide into Heteroaromatic Frameworks,CHEMISTRY - A EUROPEAN JOURNAL, Issue 45 2009Masaaki Suzuki Prof. Abstract The Pd0 -mediated rapid trapping of methyl iodide with an excess amount of a heteroaryl-substituted tributylstannane has been investigated with the aim of incorporating a short-lived 11C-labelled methyl group into the heteroaromatic carbon frameworks of important organic compounds, such as drugs with various heteroaromatic structures, in order to execute a positron emission tomography (PET) study of vital systems. The reaction was first performed by using our previously developed CH3I/stannane/[Pd2(dba)3]/P(o -CH3C6H4)3/CuCl/K2CO3 (1:40:0.5:2:2:2) system in DMF at 60,°C for 5,min (conditions A), however, the reaction gave low yields for various heteroaromatic compounds. Increasing the amount of phosphine ligand (conditions B) led to a significant improvement in the yield, but the conditions were still not suitable for a range of basic heteroaromatic structures. Use of the CuBr/CsF system (conditions C) also provided a result similar to that obtained under conditions B with an increased amount of the phosphine. Thus, pyridine and related heteroaromatic compounds remained less reactive substrates. The problem was overcome by replacing the DMF solvent with N -methyl-2-pyrolidinone (NMP). The reaction in NMP at 60,100,°C for 5,min using a CH3I/stannane/[Pd2(dba)3]/P(o -CH3C6H4)3/CuBr/CsF (1:40:0.5:16:2:5) combination (conditions D) gave the methylated products in yields of more than 80,% (based on the reaction of CH3I) for all of the heteroaromatic compounds listed in this study. Thus, the combined use of NMP and an increased amount of phosphine is important for promoting the reaction efficiently. The use of this general approach to rapid methylation has been well demonstrated by the synthesis of the PET tracers 2- and 3-[11C]methylpyridines by using [Pd2(dba)3]/P(o -CH3C6H4)3/CuBr/CsF (1:16:2:5) in NMP at 60,°C for 5,min, which gives the desired products in HPLC analytical yields of 88 and 91,%, respectively. [source] | ||||||||||