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Synthesis and preliminary studies of a novel negative allosteric modulator [11C]QCA for imaging of metabotropic glutamate receptor 2
https://repo.qst.go.jp/records/48948
https://repo.qst.go.jp/records/4894886ffbc92-05c6-485c-a7dd-1eceff871fdf
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-05-11 | |||||
| タイトル | ||||||
| タイトル | Synthesis and preliminary studies of a novel negative allosteric modulator [11C]QCA for imaging of metabotropic glutamate receptor 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 |
Zhang, Xiaofei
× Zhang, Xiaofei× Kumata, Katsushi× Yamasaki, Tomoteru× Cheng, Ran× Hatori, Akiko× Ma, Longle× Zhang, Yiding× Xie, Lin× Wang, Lu× Jin, Kang Hye× J., Sheffler Douglas× D., P. Cosford Nicholas× Zhang, Ming-Rong× H.Liang, Steven× 熊田 勝志× 山崎 友照× 羽鳥 晶子× 張 一鼎× 謝 琳× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Metabotropic glutamate 2 receptors (mGlu2) are involved in the pathogenesis of several CNS disorders and neurodegenerative diseases. Pharmacological modulation of this target represents a potential disease-modifying approach for the treatment of substance abuse, depression, schizophrenia and dementias. While quantification of mGlu2 receptors in the living brain by positron emission tomography (PET) would help us better understand signaling pathways relevant to these conditions, few successful examples have been demonstrated to image mGlu2 in vivo and a suitable PET tracer is yet to be identified. Herein we report the design and synthesis of a radiolabeled negative allosteric modulator (NAM) for mGlu2 PET tracer development based on a quinoline 2-carboxamide scaffold. The most promising candidate, 7-((2,5-dioxopyrrolidin-1-yl)methyl)-4-(2-fluoro-4- [11C]methoxyphenyl) quinoline-2-carboxamide ([11C]QCA) was prepared in 13% radiochemical yield (non-decay corrected at the end of synthesis) with >99% radiochemical purity and >74 GBq/μmol (2 Ci/μmol) specific activity. While the tracer showed limited brain uptake (0.3 SUV), probably attributable to effects on PgP/Bcrp eff lux pump, in vitro autoradiography studies demonstrated heterogeneous brain distribution and specific binding. Thus, [11C]QCA is a chemical probe that |
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| 書誌情報 |
ACS Chemical Neuroscience 巻 8, 号 9, p. 1937-1948, 発行日 2017-05 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1948-7193 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 28565908 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/acschemneuro.7b00098 | |||||
