@article{oai:repo.qst.go.jp:00046584,
 author = {Shimoda, Yoko and Yui, Joji and Xie, Lin and Fujinaga, Masayuki and Yamasaki, Tomoteru and Ogawa, Masanao and Nengaki, Nobuki and Kumata, Katsushi and Hatori, Akiko and Kawamura, Kazunori and Zhang, Ming-Rong and 由井 譲二 and 謝 琳 and 藤永 雅之 and 山崎 友照 and 小川 政直 and 念垣 信樹 and 熊田 勝志 and 羽鳥 晶子 and 河村 和紀 and 張 明栄},
 issue = {17},
 journal = {Bioorganic & Medicinal Chemistry},
 month = {Jun},
 note = {1-[2-(4-Methoxyphenyl)phenyl]piperazine (4) is a potent serotonin 5-HT7 receptor antagonist (Ki = 2.6 nM) with a low binding affinity for the 5-HT1A receptor (Ki = 476 nM). As a potential positron emission tomography (PET) radiotracer for the 5-HT7 receptor, [11C]4 was synthesized at high radiochemical yield and specific activity, by O-[11C]methylation of 2'-(piperazin-1-yl)-[1,1'-biphenyl]-4-ol (6) with [11C]methyl iodide. Autoradiography revealed that [11C]4 showed in vitro specific binding with 5-HT7 in the rat brain regions, such as the thalamus which is a region with high 5-HT7 expression. Metabolite analysis indicated that intact [11C]4 in the brain exceeded 90% of the radioactive components at 15 min after the radiotracer injection, although two radiolabeled metabolites were found in the rat plasma. The PET study of rats showed moderated uptake of [11C]4 in the brain (1.2 SUV), but no significant regional difference in radioactivity in the brain. Pretreatment with 5-HT7-selective antagonist SB269970 (3) did not decrease the uptake of [11C]4 in the rat brain. Further studies are warranted that focus on the development of PET ligand candidates with higher binding affinity for 5-HT7 and higher in vivo stability in brain than 4.
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 pages = {5316--5322},
 title = {Synthesis and Evaluation of 1-[2-(4-[11C]Methoxyphenyl)phenyl]piperazine for Imaging of the Serotonin 5-HT7 Receptor in the Rat Brain},
 volume = {21},
 year = {2013}
}