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A novel monoacylglycerol lipase-targeted 18F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network
https://repo.qst.go.jp/records/86108
https://repo.qst.go.jp/records/8610882a2f0c6-a80f-4fbe-812d-c062296f7df1
| 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 | A novel monoacylglycerol lipase-targeted 18F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network | |||||
| 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 |
Ran Cheng
× Ran Cheng× Masayuki, Fujinaga× Yang, Jing× Rong, Jian× Haider, Ahmed× Ogasawara, Daisuke× S. Van, Richard× Shao, Tuo× Chen, Zhen× Zhang, Xiaofei× R. Calderon Leon, Erick× Zhang, Yiding× Wakana, Mori× Katsushi, Kumata× Tomoteru, Yamasaki× Lin, Xie× Lu, Wang× Ran, Chongzhao× Shao, Yihan× Cravatt, Benjamin× Josephson, Lee× Zhang, Ming-Rong× Liang, Huan× Masayuki, Fujinaga× Zhang, Yiding× Wakana, Mori× Katsushi, Kumata× Tomoteru, Yamasaki× Lin, Xie× Lu, Wang× Zhang, Ming-Rong× Liang, Huan |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Monoacylglycerol lipase (MAGL) constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA). As such, selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders, metabolic diseases and cancer. Herein, we developed a reversible MAGL PET ligand, [18F]FEPAD ([18F]4), that is based on a unique 4-piperidinyl azetidine diamide scaffold. The pharmacokinetics and binding specificity revealed an outstanding specificity and selectivity towards MAGL in brown adipose tissue (BAT) – a tissue that is known to be metabolically active. We employed [18F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits and found a remarkable degree of specific tracer binding in the BAT, which was confirmed by post-mortem tissue analysis. Given the negative regulation of endocannabinoids on the metabolic BAT activity, our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders. Further, we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits, thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system (ECS)-related pathologies. KEYWORDS: monoacylglycerol lipase (MAGL); positron emission tomography (PET); diagnostic imaging; fluorine-18; brown adipose tissue (BAT) |
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| 書誌情報 |
Acta Pharmacoligica Sinica 発行日 2022-05 |
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| 出版者 | ||||||
| 出版者 | Springer Nature | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1671-4083 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1038/s41401-022-00912-8 | |||||
