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Radiosynthesis and evaluation of new PET ligands for peripheral cannabinoid receptor type 1 imaging
https://repo.qst.go.jp/records/48327
https://repo.qst.go.jp/records/48327fbc30a65-ff6e-4bbe-9a91-fa518cdea50d
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-09-21 | |||||
| タイトル | ||||||
| タイトル | Radiosynthesis and evaluation of new PET ligands for peripheral cannabinoid receptor type 1 imaging | |||||
| 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 |
Yamasaki, Tomoteru
× Yamasaki, Tomoteru× Fujinaga, Masayuki× Shimoda, Yoko× Mori, Wakana× Zhang, Yiding× Wakizaka, Hidekatsu× Ogawa, Masanao× Zhang, Ming-Rong× 山崎 友照× 藤永 雅之× 下田 陽子× 森 若菜× 張 一鼎× 脇坂 秀克× 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 | Cannabinoid receptor type 1 (CB1) is mainly expressed in the brain, as well as being expressed in functional relevant concentrations in various peripheral tissues. 1-(4-Chlorophenyl)-3-(3-(6-(pyrrolidin-1-yl)pyridin-2-yl)phenyl)urea (PSNCBAM-1, 1) was developed as a potent allosteric antagonist for CB1 and its oral administration led to reductions in the appetite and body weight of rats. Several analogs of 1 (compounds 2 and 3) were recently identified through a series of structure-activity relationship studies. Herein, we report the synthesis of radiolabeled analogs of these compounds using [11C]COCl2, and an evaluation of their potential as PET ligands for CB1 imaging using in vitro and in vivo techniques. [11C]2 and [11C]3 were successfully synthesized in two steps using [11C]COCl2. The radiochemical yields of [11C]2 and [11C]3 were 17 ± 8% and 20 ± 9% (decay-corrected to the end of bombardment, based on [11C]CO2). The specific activities of [11C]2 and [11C]3 were 42 ± 36 and 37 ± 13 GBq/μmol, respectively. The results of an in vitro binding assay using brown adipose tissue (BAT) homogenate showed that the binding affinity of 2 for CB1 (KD = 15.3 µM) was much higher than that of 3 (KD = 26.0 µM). PET studies with [11C]2 showed a high uptake of radioactivity in BAT, which decreased considerably in animals pretreated with AM281 (a selective allosteric antagonist for CB1). In conclusion, [11C]2 may be a useful PET ligand for imaging peripheral CB1 in BAT. 2009 Elsevier Ltd. All rights reserved. |
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| 書誌情報 |
Bioorganic & Medicinal Chemistry Letters 巻 27, 号 17, p. 4114-4117, 発行日 2017-07 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0960-894X | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 28757061 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.bmcl.2017.07.040 | |||||
