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Synthesis of [11C]carbonyl-labeled cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate ([11C-carbonyl]PK68) as a potential PET tracer for receptor-interacting protein 1 kinase
https://repo.qst.go.jp/records/86117
https://repo.qst.go.jp/records/861172a7abccc-ab14-43ec-b703-f4235540f8b3
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-04-07 | |||||
| タイトル | ||||||
| タイトル | Synthesis of [11C]carbonyl-labeled cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate ([11C-carbonyl]PK68) as a potential PET tracer for receptor-interacting protein 1 kinase | |||||
| 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 |
Tomoteru, Yamasaki
× Tomoteru, Yamasaki× Katsushi, Kumata× Atsuto, Hiraishi× Zhang, Yiding× Hidekatsu, Wakizaka× Kurihara, Yusuke× Nobuki, Nengaki× Zhang, Ming-Rong× Tomoteru, Yamasaki× Katsushi, Kumata× Atsuto, Hiraishi× Zhang, Yiding× Hidekatsu, Wakizaka× Kurihara, Yusuke× Nobuki, Nengaki× Zhang, Ming-Rong |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Background: Receptor-interacting protein 1 kinase (RIPK1) is a key enzyme in the regulation of cellular necroptosis. Recently, cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate (PK68, 5) has been developed as a potent inhibitor of RIPK1. Herein, we synthesized [11C]carbonyl-labeled PK68 ([11C-carbonyl]PK68, [11C]PK68) as a potential PET tracer for imaging RIPK1 and evaluated its brain uptake in vivo. Results: We synthesized [11C]PK68 by reacting amine precursor 14 with [11C]acetyl chloride. At the end of synthesis, we obtained [11C]PK68 of 1200–1790 MBq with a radiochemical yield of 9.1 ± 5.9 % (n = 10, decay-corrected to the end of irradiation) and radiochemical purity of >99%, and a molar activity of 37–99 GBq/μmol starting from 18–33 GBq of [11C]CO2. The fully automated synthesis took 30 min from the end of irradiation. In a small-animal PET study, [11C]PK68 was rapidly distributed in the liver and kidneys of healthy mice after injection, and subsequently cleared from their bodies via hepatobiliary excretion and the intestinal reuptake pathway. Although there was no obvious specific binding of RIPK1 in the PET study, [11C]PK68 demonstrated relatively high stability in vivo and provided useful structural information further candidate development. Conclusions: In the present study, we successfully radiosynthesized [11C]PK68 as a potential PET tracer and evaluated its brain uptake. We are planning to optimize the chemical structure of [11C]PK68 and conduct further PET studies on it using pathological models. |
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| 書誌情報 |
EJNMMI Radiopharmacy and Chemistry 巻 7, 号 4, p. 1-17, 発行日 2022-03 |
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| 出版者 | ||||||
| 出版者 | Springer Open | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2365-421X | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1186/s41181-022-00156-1 | |||||
| 関連サイト | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1186/s41181-022-00156-1 | |||||
