@article{oai:repo.qst.go.jp:00047064,
 author = {Tiwari, Anjani and Yui, Joji and Pooja, Singh and Agrawal, Swati and Yamasaki, Tomoteru and Xie, Lin and Chadha, Nidhi and Zhang, Yiding and Fujinaga, Masayuki and Shimoda, Yoko and Kumata, Katsushi and Anil, K Mishra and Ogawa, Masanao and Zhang, Ming-Rong and ティワリ アンジャニ and 由井 譲二 and 山崎 友照 and 謝 琳 and 張 一鼎 and 藤永 雅之 and 下田 陽子 and 熊田 勝志 and 小川 政直 and 張 明栄},
 issue = {25},
 journal = {RSC Advances},
 month = {Feb},
 note = {The 5-HT7 receptor is a recently cloned G-protein-coupled receptor (GPCR) that is important in regulating
sleep, depression, and circadian rhythms. However, the potential pathophysiological roles of 5-HT7 have
not been fully elucidated, and no 5-HT7 positron emission tomography (PET) radioligands are available,
thus limiting imaging studies of this receptor in humans. Here, we present the radiosynthesis and
biological evaluation of 5-(4-([11C]methoxyphenyl)-1-methyl-4-nitro-1H-imidazole ([11C]1) as a new PET
ligand for 5-HT7. Three-dimensional pharmacophore evaluation and docking studies confirmed its high
affinity for 5-HT7, and in vitro binding assays showed that the binding affinity was 16.8   0.9 nM. The
specific activity was found to be 48   29 GBq mmol 1 for [11C]1 in a synthetic time of 26   3 min (n ¼ 8),
having 38   7% radiochemical yield (decay-corrected) based on [11C]CO2. Ligand interactions with
human serum albumin were studied by fluorescence quenching to obtain a Stern–Volmer plot, which
showed a binding constant of 1.15   104 M 1. Whole-body biodistribution patterns were evaluated in
normal mice by 1 h dynamic PET imaging; this analysis showed rapid clearance of radioactivity from the
main peripheral organs, with the exception of the liver. Preliminary PET studies in rat brains showed rapid
accumulation of radioactivity in the brain. The regional radioactivity reached a maximum within 0–2 min
after the radioligand injection and then decreased rapidly, resulting in minimal radiation burden in the
brain during the scan. In summary, this specific biaryl system has shown potential as a 5-HT7 ligand and
further optimization and longitudinal studies may yield the first small molecule-based PET ligand for
5-HT7 in clinical settings.},
 pages = {19752--19759},
 title = {Design, synthesis and biological evaluation of small molecule based PET radioligand for 5-HT7 receptor},
 volume = {5},
 year = {2015}
}