@article{oai:repo.qst.go.jp:00047439,
 author = {Wang, Lu and Yui, Joji and Wang, Qifan and Zhang, Yiding and Mori, Wakana and Shimoda, Yoko and Fujinaga, Masayuki and Kumata, Katsushi and Yamasaki, Tomoteru and Hatori, Akiko and H, Rotstein Benjamin and Lee, Collier Thomas and Ran, Chongzhao and Vasdev, Neil and Zhang, Ming-Rong and H, Liang Steven and 由井 譲二 and 張 一鼎 and 森 若菜 and 下田 陽子 and 藤永 雅之 and 熊田 勝志 and 山崎 友照 and 羽鳥 晶子 and 張 明栄},
 issue = {1},
 journal = {ACS chemical neuroscience},
 month = {Oct},
 note = {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.},
 pages = {109--118},
 title = {Synthesis and Preliminary PET Imaging Studies of a FAAH Radiotracer ([(11)C]MPPO) Based on α-Ketoheterocyclic Scaffold.},
 volume = {7},
 year = {2015}
}