@article{oai:repo.qst.go.jp:00075870,
 author = {Hattori, Yasushi and Aoyama, Kazunobu and Maeda, Jun and Arimura, Naoto and Takahashi, Yasuko and Sasaki, Masako and Fujinaga, Masayuki and Seki, Chie and Nagai, Yuji and Kawamura, Kazunori and Yamasaki, Tomoteru and Ming-Rong, Zhang and Higuchi, Makoto and Koike, Tatsuki and Hattori, Yasushi and Maeda, Jun and Fujinaga, Masayuki and Seki, Chie and Nagai, Yuji and Kawamura, Kazunori and Yamasaki, Tomoteru and Ming-Rong, Zhang and Higuchi, Makoto},
 issue = {5},
 journal = {Journal of medicinal chemistry},
 month = {Feb},
 note = {Monoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase involved in endocannabinoid and inflammatory signaling. Positron-emission tomography (PET) imaging of MAGL serves to validate target engagement of therapeutic MAGL inhibitors as well as to investigate MAGL levels under normal and disease conditions. However, PET radioligands with reversible binding kinetics for MAGL, which allow quantitative assessment of MAGL, are hitherto unavailable. In this study, we designed and synthesized fluoro-containing PET probes starting from a recently identified piperazinyl pyrrolidine-2-one derivative with reversible binding to MAGL. By tailoring the lipophilicity of the molecule to optimize nonspecific binding and blood-brain barrier permeability, we successfully identified two compounds that show high uptake to regions enriched with MAGL. PET imaging of wild-type and MAGL-deficient mice as well as a macaque monkey indicated that [F]5 ((4 R)-1-{3-[2-(F)fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]pyrrolidin-2-one, [F]T-401) specifically binds to MAGL with adequate reversibility, yielding a high contrast for MAGL within an appropriate imaging time.},
 pages = {2362--2375},
 title = {Design, Synthesis, and Evaluation of (4 R)-1-{3-[2-(F)Fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbonyl)piperazin-1-yl]pyrrolidin-2-one ([F]T-401) as a Novel Positron-Emission Tomography Imaging Agent for Monoacylglycerol Lipase.},
 volume = {62},
 year = {2019}
}