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Quantification of monoacylglycerol lipase and its occupancy by an exogenous ligand in rhesus monkey brains using [18F]T-401 and PET
https://repo.qst.go.jp/records/84437
https://repo.qst.go.jp/records/84437e275a159-0198-4d40-a3f0-06852cd2ab3d
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-11-09 | |||||
| タイトル | ||||||
| タイトル | Quantification of monoacylglycerol lipase and its occupancy by an exogenous ligand in rhesus monkey brains using [18F]T-401 and PET | |||||
| 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 |
Hattori, Yasushi
× Hattori, Yasushi× Chie Seki× Jun, Maeda× Yuji, Nagai× Aoyama, Kazunobu× Zhang, Ming-Rong× Takafumi, Minamimoto× Koike, Tatsuki× Makoto, Higuchi× Chie, Seki× Jun, Maeda× Yuji, Nagai× Zhang, Ming-Rong× Takafumi, Minamimoto× Makoto, Higuchi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Monoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase that cleaves monoacylglycerols into fatty acids and is a potential target for the novel treatment of CNS disorders related to the endocannabinoid system and neuroinflammation. We have developed [18F]T-401 as a selective Positron emission tomography (PET) imaging agent for MAGL. In this study, we determined an analytical method to quantify MAGL availability and its occupancy by an exogenous inhibitor in rhesus monkey brains using [18F]T-401-PET. In rhesus monkeys, regional time-activity curves were described well when using an extended 2-tissue compartment model that accommodated the formation of a radiometabolite in the brain. This model yielded reliable estimates of the total distribution volume (VT), and the rank order of VT was consistent with known regional activity of MAGL enzyme in primates. The pretreatment of monkeys with JW642 resulted in a dose-dependent reduction of [18F]T-401 retentions in the brain, and VT. Lassen's graphical analysis indicated a VND of 0.69 mL/cm3 and a plasma JW642 concentration of 126 ng/mL for inhibiting the specific binding by 50%. [18F]T-401 and the method established can be used for quantification of MAGL in healthy brain and in disease conditions, and is suitable for evaluations of target engagement at cerebral MAGL | |||||
| 書誌情報 |
Journal of Cerebral Blood Flow & Metabolism p. 271678X211058285, 発行日 2021-11 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0271-678X | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 34727758 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1177/0271678X211058285 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://journals.sagepub.com/doi/10.1177/0271678X211058285 | |||||
