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Synthesis and Preliminary PET Imaging Studies of a FAAH Radiotracer ([(11)C]MPPO) Based on α-Ketoheterocyclic Scaffold.
https://repo.qst.go.jp/records/47439
https://repo.qst.go.jp/records/4743948bfd6a5-2a8a-4381-be96-57e531a3ac99
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2016-07-05 | |||||
| タイトル | ||||||
| タイトル | Synthesis and Preliminary PET Imaging Studies of a FAAH Radiotracer ([(11)C]MPPO) Based on α-Ketoheterocyclic Scaffold. | |||||
| 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 |
Wang, Lu
× Wang, Lu× Yui, Joji× Wang, Qifan× Zhang, Yiding× Mori, Wakana× Shimoda, Yoko× Fujinaga, Masayuki× Kumata, Katsushi× Yamasaki, Tomoteru× Hatori, Akiko× H, Rotstein Benjamin× Lee, Collier Thomas× Ran, Chongzhao× Vasdev, Neil× Zhang, Ming-Rong× H, Liang Steven× 由井 譲二× 張 一鼎× 森 若菜× 下田 陽子× 藤永 雅之× 熊田 勝志× 山崎 友照× 羽鳥 晶子× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Fatty acid amide hydrolase (FAAH) is one of the principle enzymes for metabolizing endogenous cannabinoid neurotransmitters such as anandamide, and thus regulates endocannabinoid (eCB) signaling. Selective pharmacological blockade of FAAH has emerged as a potential therapy to discern the endogenous functions of anandamide-mediated eCB pathways in anxiety, pain, and addiction. Quantification of FAAH in the living brain by positron emission tomography (PET) would help our understanding of the endocannabinoid system in these conditions. While most FAAH radiotracers operate by an irreversible ("suicide") binding mechanism, a FAAH tracer with reversibility would facilitate quantitative analysis. We have identified and radiolabeled a reversible FAAH inhibitor, 7-(2-[(11)C]methoxyphenyl)-1-(5-(pyridin-2-yl)oxazol-2-yl)heptan-1-one ([(11)C]MPPO) in 13% radiochemical yield (nondecay corrected) with >99% radiochemical purity and 2 Ci/μmol (74 GBq/μmol) specific activity. The tracer showed moderate brain uptake (0.8 SUV) with heterogeneous brain distribution. However, blocking studies with a potent FAAH inhibitor URB597 demonstrated a low to modest specificity to the target. Measurement of lipophilicity, metabolite, and efflux pathway analysis were also performed to study the pharmacokinetic profile of [(11)C]MPPO. In all, we reported an efficient radiolabeling and preliminary evaluation of the first-in-class FAAH inhibitor [(11)C]MPPO with α-ketoheterocyclic scaffold. | |||||
| 書誌情報 |
ACS chemical neuroscience 巻 7, 号 1, p. 109-118, 発行日 2015-10 |
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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 | 26505525 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/acschemneuro.5b00248 | |||||
