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Design, synthesis and biological evaluation of small molecule based PET radioligand for 5-HT7 receptor
https://repo.qst.go.jp/records/47064
https://repo.qst.go.jp/records/47064fcb10d10-8d13-406b-96c3-d56db80bbfc4
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-03-25 | |||||
| タイトル | ||||||
| タイトル | Design, synthesis and biological evaluation of small molecule based PET radioligand for 5-HT7 receptor | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Tiwari, Anjani
× Tiwari, Anjani× Yui, Joji× Pooja, Singh× Agrawal, Swati× Yamasaki, Tomoteru× Xie, Lin× Chadha, Nidhi× Zhang, Yiding× Fujinaga, Masayuki× Shimoda, Yoko× Kumata, Katsushi× Anil, K Mishra× Ogawa, Masanao× Zhang, Ming-Rong× ティワリ アンジャニ× 由井 譲二× 山崎 友照× 謝 琳× 張 一鼎× 藤永 雅之× 下田 陽子× 熊田 勝志× 小川 政直× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. |
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| 書誌情報 |
RSC Advances 巻 5, 号 25, p. 19752-19759, 発行日 2015-02 |
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