594847-99-1Relevant academic research and scientific papers
Synthesis of an18F-fluorobenzoate idarubicin derivative as new potential PET radiotracer to predict chemotherapy resistance
Seimbille, Yann,Czernin, Johannes,Phelps, Michael E.,Silverman, Daniel H. S.
, p. 819 - 827 (2005)
Anthracyclines are among the most widely used antineoplastic agents in current clinical practice. Nevertheless, chemoresistance, which results in failure to eradicate the tumor, is often observed after administration of anthracyclines, and no assay system
Development of fluorine-18-labeled 5-HT(1A) antagonists
Lang, Lixin,Jagoda, Elaine,Schmall, Bernard,Vuong, Bik-Kee,Adams, H. Richard,Nelson, David L.,Carson, Richard E.,Eckelman, William C.
, p. 1576 - 1586 (2007/10/03)
We have synthesized five fluorinated derivatives of WAY 100635, N-{2- [4-(2-methoxyphenyl)piperazino]ethyl)-N-(2-pyridyl)cyclohexanecarboxamide (4a), using various acids in place of the cyclohexanecarboxylic acid (CHCA, 2a) in the reaction scheme. The five acids are 4-fluorobenzoic acid (FB, 2b), 4-fluoro-3-methylbenzoic acid (MeFB, 2c), trans-4- fluorocyclohexanecarboxylic acid (FC, 2d), 4-(fluoromethyl)benzoic acid (FMeB, 2e), and 3-nitro-4(fluoromethyl)benzoic acid (NFMeB, 2f) (see Scheme 1). These compounds were radiolabeled with fluorine-18, and their biological properties were evaluated in rats and compared with those of [11C]carbonyl WAY 100635 ([carbonyl-11C]4a). [Carbonyl-11C]4a cleared the brain with a biological half-life averaging 41 min. The metabolite-corrected blood radioactivity had a half-life of 29 min. [18F]FCWAY ([18F]4d) gave half- lives and intercepts comparable to [carbonyl11C]4a in the brain, but the blood clearance was faster. [18F]FBWAY ([18F]4b) showed an early rapid net efflux from the whole brain, clearing with a biological half-life of 35 min. The metabolite-corrected blood half-life was 41 min. The comparable whole brain and blood half-lives for Me[18F]FBWAY ([18F]4c) were 16 and 18 min, respectively. For each compound, the corresponding carboxylic acid was identified as a major metabolite in blood. Fluoride was also found after injection of [18F]4d. However, for all compounds there was a good correlation (R > 0.97) between the differential uptake ratio (DUR, (%ID/g) x body weight (g)/100) in individual rat brain regions at 30 min after injection and the concentration of receptors as determined by in vitro quantitative autoradiography in rat. Specific binding ratios [region of interest (ROI)/cerebellum-1] in control studies for cortex (Ctx) and hippocampus (H) were higher for [carbonyl11C]4a and [18F]4d compared to [18F]4b and [18F]4c. [18F]4d has similar pharmacokinetic properties and comparable specific binding ratios to [carbonyl-11C]4a. Fifty nanomoles of 4a blocked only 30% of the specific binding of [18F]4d, while complete blockade was obtained from co-injection of 200 nmol of 4a (H/Cb-1 from 17.2 to 0.6). [18F]4b and [18F]4c showed lower specific binding ratios than [carbonyl-11C]4a and [18F]4d. [18F]4c was superior to [18F]4b since its specific binding was more readily blocked by 4a. These studies suggest that [18F]4c should be a useful compound to assess dynamic changes in serotonin levels while [18F]4d, with its high contrast and F-18 label, should provide better statistics and quantification for static measurement of 5-HT(1A) receptor distribution.
