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Radiosynthesis and evaluation of 4-(6-[18F]Fluoro-4-(5-isopropoxy-1H-indazol-3-yl)pyridin-2-yl)morpholine as a novel radiotracer candidate targeting leucine-rich repeat kinase 2
https://repo.qst.go.jp/records/80109
https://repo.qst.go.jp/records/80109993f1933-6ef7-471c-b5f8-0e5f2c54a26f
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-06-22 | |||||
| タイトル | ||||||
| タイトル | Radiosynthesis and evaluation of 4-(6-[18F]Fluoro-4-(5-isopropoxy-1H-indazol-3-yl)pyridin-2-yl)morpholine as a novel radiotracer candidate targeting leucine-rich repeat kinase 2 | |||||
| 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 |
Mori, Wakana
× Mori, Wakana× Yamasaki, Tomoteru× Hattori, Yasushi× Zhang, Yiding× Kumata, Katsushi× Fujinaga, Masayuki× Hanyu, Masayuki× Nengaki, Nobuki× Zhang, Hong× Ming-Rong, Zhang× Mori, Wakana× Yamasaki, Tomoteru× Hattori, Yasushi× Zhang, Yiding× Kumata, Katsushi× Fujinaga, Masayuki× Hanyu, Masayuki× Nengaki, Nobuki× Ming-Rong, Zhang |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Mutations that increase leucine-rich repeat kinase 2 (LRRK2) activity in the brain are associated with Parkinson's disease. Here, we synthesized a novel compound 4-(6-fluoro-4-(5-isopropoxy-1H-indazol-3-yl)pyridin-2-yl)morpholine (FIPM) and labeled it with fluorine-18 (18F), to develop a positron emission tomography (PET) tracer for in vivo visualization of LRRK2 in the brain. FIPM showed high in vitro binding affinity for LRRK2 (IC50 = 8.0 nM). [18F]FIPM was prepared in 5% radiochemical yield (n = 5), by inserting 18F into a pyridine ring, followed by removal of the protecting group. After HPLC separation and formulation, [18F]FIPM was acquired with >97% radiochemical purity and 103–300 GBq μmol−1 of molar activity at the end of radiosynthesis. Biodistribution and small-animal PET studies in mice indicated a low in vivo specific binding of [18F]FIPM. While [18F]FIPM presented limited potential as an in vivo PET tracer for LRRK2, we suggested that it can be used as a lead compound for developing new radiotracers with improved in vivo brain properties. | |||||
| 書誌情報 |
RSC Medicinal Chemistry 巻 11, p. 676-684, 発行日 2020-05 |
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| 出版者 | ||||||
| 出版者 | Royal Society of Chemistry | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2040-2503 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1039/c9md00590k | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://pubs.rsc.org/en/content/articlelanding/2020/md/c9md00590k#!divAbstract | |||||
