Saigal, Neil; Pichika, Rama; Easwaramoorthy, Balasubramaniam; Collins, Daphne; Christian, Bradley T.; Shi, Bingzhi; Narayanan, Tanjore K.; Potkin, Steven G.; Mukherjee, Jogeshwar published the artcile< Synthesis and biologic evaluation of a novel serotonin 5-HT1A receptor radioligand, 18F-labeled mefway, in rodents and imaging by PET in a nonhuman primate>, Reference of 112-63-0, the main research area is serotonin 5HT1A receptor fluorine 18 mefway PET.
Serotonin 5-HT1A receptors have been implicated in disorders of the central nervous system and, therefore, are being studied by PET. Efforts are under way to improve in vivo stability of 5-HT1A agents currently in human use (11C-labeled N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-(2-pyridinyl)cyclohexanecarboxamide [11C-WAY-100635]), 4-(2′-methoxyphenyl)-1-[2′-(N-2”-pyridinyl)-p-18F-fluorobenzamido]ethylpiperazine [18F-MPPF], and 18F-labeled trans-4-fluoro-N-(2-[4-(2-methoxyphenyl)piperazin-1-yl)ethyl]-N-(2-pyridyl)cyclohexanecarboxamide) [18F-FCWAY]. We have synthesized N-{2-[4-(2-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4-18F-fluoromethylcyclohexane)carboxamide (18F-mefway), which contains a 18F on a primary carbon to make the compound more stable to defluorination. Methods: Radiosynthesis of 18F-mefway was performed in a single tosylate for 18F-fluoride exchange. In vitro binding studies on rat brain slices using 18F-mefway were read on a phosphor imager. Monkey PET studies were performed on a whole-body PET scanner. Results: Binding affinity (inhibitory concentration of 50% [IC50]) of mefway was 26 nmol/L and was comparable to that of WAY-100635, 23 nmol/L. Yields of 18F-mefway were 20%-30% in specific activities of 74-111 GBq/μmol at the end of synthesis. In vitro binding of 18F-mefway in the hippocampus (Hp), colliculus (Co), cortex (Ctx), and other brain regions-with limited binding in the cerebellum (Cer)-was observed, with ratios of Hp/Cer = 82.3, Co/Cer = 45.8, and Ctx/Cer = 40. Serotonin displaced 18F-mefway from various brain regions with IC50 values in the range of 169-243 nmol/L. PET studies in a rhesus monkey showed 18F-mefway binding in the fontal cortex (FC), temporal cortex (TC) including hippocampus, raphe (Rp), and other brain regions, with ratios of FC/Cer = 9.0, TC/Cer = 10, and Rp/Cer = 3.3. Plasma anal. indicated the presence of approx. 30% of 18F-mefway at 150-180 min after injection. Conclusion: The high ratios in specific brain regions such as the hippocampus suggest that 18F-mefway has potential as a PET agent for 5HT1A receptors.
Journal of Nuclear Medicine published new progress about 5-HT1A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Reference of 112-63-0.
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