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1.
《Bioorganic & medicinal chemistry letters》2019,29(13):1654-1659
To develop PET tracers for imaging of neuroinflammation, new carbon-11-labeled sEH/PDE4 dual inhibitors have been synthesized. The reference standard N-(4-methoxy-2-(trifluoromethyl)benzyl)benzamide (1) and its corresponding desmethylated precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)benzamide (2) were synthesized from (4-methoxy-2-(trifluoromethyl)phenyl)methanamine and benzoic acid in one and two steps with 84% and 49% overall chemical yield, respectively. The standard N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA, 4) and its precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (5) were synthesized from methyl 4-piperidinecarboxylate, propionyl chloride and (4-methoxy-2-(trifluoromethyl)phenyl)methanamine in two and three steps with 62% and 34% overall chemical yield, respectively. The target tracers N-(4-[11C]methoxy-2-(trifluoromethyl)benzyl)benzamide ([11C]1) and N-(4-[11C]methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide ([11C]MPPA, [11C]4) were prepared from their corresponding precursors 2 and 5 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 25–35% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (AM) at EOB was 370–740 GBq/μmol with a total synthesis time of 35–40-minutes from EOB. 相似文献
2.
Limin Wang Wenchao Qu Brian Lieberman Karl Ploessl Hank F. Kung 《Bioorganic & medicinal chemistry letters》2010,20(12):3482-3485
Three new 18F labeled fluoroalkyl tyrosine derivatives, O-(2-[18F]fluoroethyl)-α-methyltyrosine (FEMT, [18F]2), O-(2-[18F]fluoroethyl)-2-l-azatyrosine (FEAT, [18F]3), O-(2-[18F]fluoroethyl)-l-tyrosineamide (FETA, [18F]4) have been synthesized and radiofluorinated with 5–34% decay-corrected yield. In vitro studies were carried out in U-138 MG human glioblastoma. Cellular uptake of new tracers was compared to clinically utilized imaging agent O-(2-[18F]fluoroethyl)-l-tyrosine (FET, [18F]1). The uptake of tracers followed the order of FET ([18F]1) > FEAT([18F]3) > FEMT ([18F]2) ≈ FETA ([18F]4). 相似文献
3.
Vattoly J. Majo Victoria Arango Norman R. Simpson Jaya Prabhakaran Suham A. Kassir Mark D. Underwood Mihran Bakalian Peter Canoll J. John Mann J.S. Dileep Kumar 《Bioorganic & medicinal chemistry letters》2013,23(14):4191-4194
Radiosynthesis and in vitro evaluation of [18F](S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide ([18F]BMS-754807 or [18F]1) a specific IGF-1R inhibitor was performed. [18F]1 demonstrated specific binding in vitro to human cancer tissues. Synthesis of reference standard 1 and corresponding bromo derivative (1a), the precursor for radiolabeling were achieved from 2,4-dichloropyrrolo[2,1-f][1,2,4]triazine (4) in three steps with 50% overall yield. The radioproduct was obtained in 8% yield by reacting 1a with [18F]TBAF in DMSO at 170 °C at high radiochemical purity and specific activity (1–2 Ci/μmol, N = 10). The proof of concept of IGF-IR imaging with [18F]1 was demonstrated by in vitro autoradiography studies using pathologically identified surgically removed grade IV glioblastoma, breast cancer and pancreatic tumor tissues. These studies indicate that [18F]1 can be a potential PET tracer for monitoring IGF-1R. 相似文献
4.
The androgen receptor (AR) is an attractive target for the treatment and molecular imaging of prostate cancer. New carbon-11-labeled propanamide derivatives were first designed and synthesized as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging using the biomedical imaging technique positron emission tomography (PET). The target tracers, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[11C]methoxyphenoxy)-2-methylpropanamide ([11C]8a), (S)-2-hydroxy-3-(2-[11C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([11C]8e), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-[11C]methoxyphenoxy)-2-methylpropanamide ([11C]8c) and (S)-2-hydroxy-3-(4-[11C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([11C]8g), were prepared by O-[11C]methylation of their corresponding precursors, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-hydroxyphenoxy)-2-methylpropanamide (9a), (S)-2-hydroxy-3-(2-hydroxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9b), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methylpropanamide (9c) and (S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9d), with [11C]CH3OTf under basic conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method in 55 ± 5% (n = 5) radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5). 相似文献
5.
Alessandra Gaeta John Woodcraft Stuart Plant Julian Goggi Paul Jones Mark Battle William Trigg Sajinder K. Luthra Matthias Glaser 《Bioorganic & medicinal chemistry letters》2010,20(15):4649-4652
The labelling reagent 2-[18F]fluoroethylazide was used in a traceless Staudinger ligation. This reaction was employed to obtain the GABAA receptor binding 6-benzyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (2-[18F]fluoroethyl) amide. The radiotracer was prepared with a non-decay corrected radiochemical yield of 7%, a radiochemical purity >95% and a specific radioactivity of 0.9 GBq/μmol. The compound showed low brain penetration in normal rats. A series of fluoroalkyl 4-quinolone analogues with nanomolar to sub-nanomolar affinity for the GABAA receptor has been prepared as well. 相似文献
6.
《Bioorganic & medicinal chemistry》2016,24(9):2043-2052
3-[18F]Fluoro-2-hydroxypropyl substituted compounds were synthesized and evaluated as novel 18F-labeled PET tracers for imaging Aβ plaque in a living brain. All compounds exhibited high binding affinities toward the synthetic Aβ1–42 aggregate and/or Alzheimer’s disease brain homogenate. In the microPET study with normal mice, the 3-[18F]fluoro-2-hydroxypropyl substituted compounds resulted in fast brain washout by reducing the lipophilicities of the compounds. Intriguingly, (S)-configured PET tracers, (S)-[18F]1b and (S)-[18F]1c, exhibited a 2.8 and 4.0-fold faster brain washout rate at a peak/30 min in the mouse brain than the corresponding (R)-configured PET tracers despite there being no meaningful difference in binding affinities toward Aβ plaque. A further evaluation of (S)-[18F]1c with healthy rhesus monkeys also revealed excellent clearance from the frontal cortex with ratios of 7.0, 16.0, 30.0 and 49.0 at a peak/30, 60, 90, and 120 min, respectively. These results suggest that (S)-[18F]1c may be a potential PET tracer for imaging Aβ plaque in a living brain. 相似文献
7.
《Bioorganic & medicinal chemistry letters》2014,24(18):4455-4459
The reference standard AZD8931{2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)-N-methylacetamide} (11a) was synthesized from methyl 4,5-dimethoxy-2-nitrobenzoate or ethyl 4,5-dimethoxy-2-nitrobenzoate and 2-chloro-N-methylacetamide in 11 steps with 2–5% overall chemical yield. The precursor N-desmethyl-AZD8931{2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)acetamide} (11b) was synthesized from methyl 4,5-dimethoxy-2-nitrobenzoate or ethyl 4,5-dimethoxy-2-nitrobenzoate and 2-bromoacetamide in 11 steps with 2–4% overall chemical yield. The target tracer [11C]AZD8931 {2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)-N-[11C]methylacetamide} ([11C]11a) was prepared from N-desmethyl-AZD8931 (11b) with [11C]CH3OTf under basic condition (NaH) through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40–50% radiochemical yield based on [11C]CO2 and decay corrected to end of bombardment (EOB) with 370–1110 GBq/μmol specific activity at EOB. 相似文献
8.
《Bioorganic & medicinal chemistry letters》2020,30(23):127555
Selective metabotropic glutamate receptor 2 (mGluR2) inhibitors have been demonstrated to show therapeutic effects by improving alleviating symptoms of schizophrenic patients in clinical studies. Herein we report the synthesis and preliminary evaluation of a 11C-labeled positron emission tomography (PET) tracer originating from a mGluR2 inhibitor, 3-(cyclopropylmethyl)-7-((4-(4-methoxyphenyl)piperidin-1-yl)methyl)-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (CMTP, 1a). [11C]CMTP ([11C]1a) was synthesized by O-[11C]methylation of desmethyl precursor 1b with [11C]methyl iodide in 19.7 ± 8.9% (n = 10) radiochemical yield (based on [11C]CO2) with >98% radiochemical purity and >74 GBq/μmol molar activity. Autoradiography study showed that [11C]1a possessed moderate in vitro specific binding to mGluR2 in the rat brain, with a heterogeneous distribution of radioactive accumulation in the mGluR2-rich brain tissue sections, such as the cerebral cortex and striatum. PET study indicated that [11C]1a was able to cross the blood–brain barrier and enter the brain, but had very low specific binding in the rat brain. Further optimization for the chemical structure of 1a is necessary to increase binding affinity to mGluR2 and then improve in vivo specific binding in brain. 相似文献
9.
Aristeidis Chiotellis Adrienne Müller Karin Weyermann Dominique S. Leutwiler Roger Schibli Simon M. Ametamey Stefanie D. Krämer Linjing Mu 《Amino acids》2014,46(8):1947-1959
Amino acid transport is an attractive target for oncologic imaging. Despite a high demand of cancer cells for cationic amino acids, their potential as PET probes remains unexplored. Arginine, in particular, is involved in a number of biosynthetic pathways that significantly influence carcinogenesis and tumor biology. Cationic amino acids are transported by several cationic transport systems including, ATB0,+ (SLC6A14), which is upregulated in certain human cancers including cervical, colorectal and estrogen receptor-positive breast cancer. In this work, we report the synthesis and preliminary biological evaluation of a new cationic analog of the clinically used PET tumor imaging agent O-(2-[18F]fluroethyl)-l-tyrosine ([18F]FET), namely O-2((2-[18F]fluoroethyl)methylamino)ethyltyrosine ([18F]FEMAET). Reference compound and precursor were prepared by multi-step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [18F]fluorination in 16–20 % decay-corrected yields with radiochemical purity >99 %. The new tracer showed good stability in vitro and in vivo. Cell uptake assays demonstrated that FEMAET and [18F]FEMAET accumulate in prostate cancer (PC-3) and small cell lung cancer cells (NCI-H69), with an energy-dependent mechanism. Small animal PET imaging with NCI-H69 xenograft-bearing mice revealed good tumor visualization comparable to [18F]FET and low brain uptake, indicating negligible transport across the blood–brain barrier. In conclusion, the non-natural cationic amino acid PET probe [18F]FEMAET accumulates in cancer cells in vitro and in vivo with possible involvement of ATB0,+. 相似文献
10.
Tiantian Mou Huihui Jing Wenjiang Yang Wei Fang Cheng Peng Feng Guo Xianzhong Zhang Yan Pang Yunchuan Ma 《Bioorganic & medicinal chemistry》2010,18(3):1312-1320
Myocardial extractions of pyridaben, a mitochondrial complex I (MC-I) inhibitor, is well correlated with blood flow. Based on the synthesis and characterization of pyridaben analogue 2-tert-butyl-5-[2-(2-[18F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([18F]FP2OP), this study assessed its potential to be developed as myocardial perfusion imaging (MPI) agent.Methods: The tosylate labeling precursor 2-(2-(4-(tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl)benzyloxy)ethoxy)ethyl ester (OTs-P2OP) and the nonradioactive 2-tert-butyl-5-[2-(2-[19F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([19F]FP2OP) were synthesized and characterized by IR, 1H NMR, 13C NMR and MS analysis. By substituting tosyl of precursor OTs-P2OP with 18F, the radiolabeled complex [18F]FP2OP was prepared and further evaluated for its in vitro physicochemical properties, in vivo biodistribution, the metabolic stability in mice, ex vivo autoradiography and cardiac PET/CT imaging.Results: Starting with [18F]F? Kryptofix 2.2.2./K2CO3 solution, the total reaction time for [18F]FP2OP was about 100 min, with final high-performance liquid chromatography purification included. Typical decay-corrected radiochemical yield stayed at 41 ± 5.3%, the radiochemical purity, 98% or more. Biodistribution in mice showed that the heart uptake of [18F]FP2OP was 41.90 ± 4.52%ID/g at 2 min post-injection time, when the ratio of heart/liver, heart/lung and heart/blood reached 6.83, 9.49 and 35.74, respectively. Lipophilic molecule was further produced by metabolized [18F]FP2OP in blood and urine at 30 min. Ex vivo autoradiography demonstrates that [18F]FP2OP may have high affinity with MC-I and that can be blocked by [19F]FP2OP or rotenone (a known MC-I inhibitor). Cardiac PET images were obtained in a Chinese mini-swine at 5, 15, 30 and 60 min post-injection time with high quality.Conclusion: [18F]FP2OP was synthesized with high radiochemical yield. The promising biological properties of [18F]FP2OP suggest high potential as MPI agent for positron emission tomography in the future. 相似文献
11.
O. S. Fedorova O. F. Kuznetsova S. V. Shatik M. A. Stepanova Yu. N. Belokon V. I. Maleev R. N. Krasikova 《Russian Journal of Bioorganic Chemistry》2009,35(3):306-314
Tyrosine derivatives labeled with a short-lived fluorine-18 isotope (T 1/2 110 min), namely 2-[18F]fluoro-L-tyrosine (FTYR) and O-(2′-[18F]fluoroethyl)-L-tyrosine (FET), promising radiopharmaceuticals (RPs) for positron emission tomography (PET), were obtained by asymmetric syntheses. Accumulation of FTYR and FET in the rat tumor “Glioma 35 rats tumor” and in abscesses induced in Wistar rats muscles was studied and compared with that of a well-known glycolysis radiotracer 2-[18F]fluoro-2-deoxy-D-glucose (FDG). It was shown that the relative accumulation indices of amino acid RPs were considerably lower than those of FDG. At the same time, tumor/muscle ratios were high enough (2.9 for FET and 3.9 for FTYR 120 min after injection) for reliable tumor visualization. The data obtained indicated a possibility in principle to use FTYR and FET for differentiated PET diagnostics of brain tumors and inflammation lesions. Of the tyrosine derivatives studied, FET seems to be the most promising agent due to a simple and easily automated method of preparation based on direct nucleophilic substitution of the leaving tosyloxy group of an enantiomerically pure Ni-(S)-BPS-(S)-Tyr(CH2CH2OTs) precursor by an activated [18F]fluoride. 相似文献
12.
Bouvet V Wuest M Tam PH Wang M Wuest F 《Bioorganic & medicinal chemistry letters》2012,22(6):2291-2295
A new synthesis of O-(2-[18F]fluoroethyl)-l-tyrosine [18F]FET was developed using a NanoTek® microfluidic synthesis system (Advion BioSciences, Inc.). Optimal reaction conditions were studied through screening different reaction parameters like temperature, flow rate, reaction time, concentration of the labeling precursor, and the applied volume ratio between the labeling precursor and [18F]fluoride. [18F]FET was obtained after HPLC purification with 50% decay-corrected radiochemical yield starting from as little as 40 μg of labeling precursor. Small animal PET studies in EMT-6 tumor bearing mice showed radioactivity accumulation in the tumor (SUV60min 1.21 ± 0.2) resulting in an slightly increasing tumor-to-muscle ratio over time. 相似文献
13.
Katsushi Kumata Tomoteru Yamasaki Akiko Hatori Yiding Zhang Wakana Mori Masayuki Fujinaga Lin Xie Takayuki Okubo Nobuki Nengaki Ming-Rong Zhang 《Bioorganic & medicinal chemistry letters》2017,27(14):3139-3143
The purpose of this study was to develop three new radiotracers, 1-(cyclopropylmethyl)-4-([11C/18F]substituted-phenyl)piperidin-1-yl-2-oxo-1,2-dihydropyridine-3-carbonitrile ([11C]1, [11C]2, and [18F]4), and to examine their specific bindings with metabotropic glutamate receptor subtype 2 (mGluR2) in rat brain sections by using in vitro autoradiography. These compounds were found to possess potent in vitro binding affinities (Ki: 8.0–34.1 nM) for mGluR2 in rat brain homogenate. [11C]1, [11C]2, and [18F]4 were synthesized by [11C/18F]alkylation of the corresponding phenol precursors with [11C]methyl iodide or [18F]fluoroethyl bromide with >98% radiochemical purity and 80–130 GBq/μmol specific activity at the end of synthesis. In vitro autoradiography indicated that these radiotracers showed heterogeneous specific bindings in mGluR2-rich brain regions, such as the cerebral cortex, striatum, hippocampus, and granular layer of the cerebellum. 相似文献
14.
Activity in vivo and redox States in vitro of nitro- and chlorodiphenyl ether herbicide analogs 总被引:3,自引:3,他引:0
Excised cucumber (Cucumis sativus L. cv 447 Wisconsin SMR 18) cotyledons were sensitive to acifluorfen-methyl (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate) and MC-15608 (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-chlorobenzoate). Injury was detected by monitoring efflux of 3-O-methyl-d-[U-14C]glucose from herbicide-treated tissue after exposure to light. Efflux kinetics of 3-O-methyl-[14C]glucose from cotyledons treated with either acifluorfen-methyl (AFM) or MC-15608 were similar. Neither herbicide was active in darkness. 相似文献
15.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1986,13(5):523-526
There is great interest in the application of positron labeled ligands to map the dopamine receptor in vivo. A series of fluorine-18-labeled N-alkyl and N-fluoroalkyl spiroperidol (SP) derivatives N-methyl[18F]SP; N-ethyl[18F]SP; N-(2-[18F]fluoroethyl)SP; N-propyl[18F]SP; N-(3-[18F]fluoropropyl)SP; N-(3-fluoropropyl) [18F]SP; N-(2-[18F]fluoropropyl)SP; N-(2-[18F]fluorobutyl)SP; N-(2-[18F]fluoropentyl)SP; and N-(2-[18F]fluorohexyl) SP were synthesized. The lipophilicity of these ligands (log octanol/water partition coefficient) varies from 2.67 to 5.56 and the initial brain uptake in rats, measured at 2 min, was greatest with the methyl, ethyl, propyl, fluoroethyl, and fluoropropyl derivatives. The highest striatum/cerebellum values 1 h after administration were obtained with the N-methyl, N-propyl, and N-3-fluoropropyl derivatives, while that of N-2-fluoroethyl showed the greatest uptake of total activity in the brain at this time. The uptake of all these ligands in the striatum could be blocked by cold SP showing the striatal uptake to be by the dopamine receptors. 相似文献
16.
Min Wang Mingzhang Gao Zhidong Xu Qi-Huang Zheng 《Bioorganic & medicinal chemistry letters》2017,27(6):1351-1355
The reference standard (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (HG-10-102-01) and its precursor (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-hydroxyphenyl)(morpholino)methanone (desmethyl-HG-10-102-01) were synthesized from 2,4,5-trichloropyrimide and 3-methoxy-4-nitrobenzoic acid with overall chemical yield 49% in four steps and 14% in five steps, respectively. The target tracer (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-[11C]methoxyphenyl)(morpholino)methanone ([11C]HG-10-102-01) was prepared from the precursor desmethyl-HG-10-102-01 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 45–55% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370–1110 GBq/μmol with a total synthesis time of ~40-min from EOB. 相似文献
17.
《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,759(2):355-359
(S)-[18F]Fluorocarazolol is a radiopharmaceutical developed to quantitatively assess β-adrenergic receptors in vivo via positron emission tomography imaging. Since radioactive metabolites of (S)-[18F]fluorocarazolol rapidly appear in the plasma, methods for conveniently and reliably evaluating plasma for (S)-[18F]fluorocarazolol content are required. Here we present methods and validation of an approach using commercial extraction cartridges that is faster and more convenient than an approach using internal-surface reverse-phase chromatography but yields comparable results. 相似文献
18.
Xiaohong Wang Fugui Dong Caihong Miao Wei Li Min Wang Mingzhang Gao Qi-Huang Zheng Zhidong Xu 《Bioorganic & medicinal chemistry letters》2018,28(10):1836-1841
Carbon-11-labeled serotonin (5-hydroxytryptamine) 6 receptor (5-HT6R) antagonists, 1-[(2-bromophenyl)sulfonyl]-5-[11C]methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole (O-[11C]2a) and 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-[11C]methyl-1-piperazinyl)methyl]-1H-indole (N-[11C]2a), 5-[11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (O-[11C]2b) and 5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (N-[11C]2b), 1-((4-isopropylphenyl)sulfonyl)-5-[11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[11C]2c) and 1-((4-isopropylphenyl)sulfonyl)-5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1H-indole (N-[11C]2c), 1-((4-fluorophenyl)sulfonyl)-5-[11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[11C]2d) and 1-((4-fluorophenyl)sulfonyl)-5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1H-indole (N-[11C]2d), were prepared from their O- or N-desmethylated precursors with [11C]CH3OTf through O- or N-[11C]methylation and isolated by HPLC combined with SPE in 40–50% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370–740?GBq/μmol with a total synthesis time of ~40-min from EOB. 相似文献
19.
M. Zuhayra A. Alfteimi C. Von Forstner U. Lützen B. Meller E. Henze 《Bioorganic & medicinal chemistry》2009,17(21):7441-7448
O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) is one of the first 18F-labeled amino acids for imaging amino acid metabolism in tumors. This tracer overcomes the disadvantages of [18F]fluorodeoxyglucose, [18F]FDG, and [11C]methionine, [11C]MET. Nevertheless, the various synthetic methods providing 18F[FET] exhibit a big disadvantage concerning the necessity of two purification steps during the synthesis including HPLC purification, which causes difficulties in the automation, moderate yields, and long synthesis times >60 min.A new approach for the synthesis of [18F]FET is developed starting from 2-bromoethyl triflate as precursor. After optimization of the synthesis parameters including the distillation step of [18F]-FCH2CH2Br combined with the final purification of [18F]FET using a simple solid phase extraction instead of an HPLC run the synthesis [18F]FET could be significantly simplified, shortened, and improved. The radiochemical yield (RCY) was about 45% (not decay corrected and calculated relative to [18F]F− activity that was delivered from the cyclotron). Synthesis time was only 35 min from the end of bombardment (EOB) and the radiochemical purity was >99% at the end of synthesis (EOS). Thus, this simplified synthesis for [18F]FET offers a very good option for routine clinical use. 相似文献
20.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1986,13(6):617-624
No-carrier-added (NCA)3-(2′-[18F]fluoroethyl)spiperone (5), a new dopamine receptor-binding radiopharmaceutical for positron emission tomography, was synthesized by two different methods. Alkylation of the amide nitrogen in spiperone by NCA [18F]fluorobromoethane in the presence of a strong base gave 5 (Method A). Experimental methods were also developed for the syntheses of functional 3-N-alkylderivatives of spiperone such as 3-(2′-bromoethyl)- or 3-(2′-methylsulfonyloxyethyl)spiperone (4a and 4b, respectively). These derivatives (4) reacted with NCA Ag18F, Cs18F or K18F/Kryptofix 222 in acetonitrile or DMSO to give 5 (Method B). Method B, using K18F/Kryptofix 222 in acetonitrile provided 5 in multimillicure amounts (30–40% isolated radiochemical yield) with a specific activity of 2–10/μmol (EOS) in less than 60 min. This one-step, one-pot synthesis is simple, and the high radiochemical yield of 5, as well as the 110 min half-life of 18F, permit multiple tomographic studies a day with one preparation. Tomographic results in monkey brain with 5 are consistent with the labeling of dopamine-D2 receptor systems. 相似文献