@article{oai:repo.qst.go.jp:00049507,
 author = {Mori, Wakana and Yamasaki, Tomoteru and Fujinaga, Masayuki and Ogawa, Masanao and Zhang, Yiding and Hatori, Akiko and Xie, Lin and Kumata, Katsushi and Wakizaka, Hidekatsu and Kurihara, Yusuke and Ohkubo, Takayuki and Nengaki, Nobuki and Ming-Rong, Zhang and Mori, Wakana and Yamasaki, Tomoteru and Fujinaga, Masayuki and Ogawa, Masanao and Zhang, Yiding and Hatori, Akiko and Xie, Lin and Kumata, Katsushi and Wakizaka, Hidekatsu and Kurihara, Yusuke and Ohkubo, Takayuki and Nengaki, Nobuki and Ming-Rong, Zhang},
 issue = {2},
 journal = {Jounal of Medicinal Chemistry},
 month = {Dec},
 note = {Phosphodiesterase 10A (PDE10A) is a newly identified therapeutic target for central nervous system disorders. 2-(2-(3-(4-([18F]Fluoroethoxy)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]MNI-659, [18F]5) is a useful positron emission tomography (PET) ligand for imaging of PDE10A in the human brain. However, the radiolabeled metabolite of [18F]5 can accumulate in the brain. In this study, using [18F]5 as a lead compound, we designed four new 18F-labeled ligands ([18F]6–9) to find one more suitable than [18F]5. Of these, 2-(2-(3-(4-([18F]fluoromethoxy-d2)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]9) exhibited high in vitro binding affinity (Ki = 2.9 nM) to PDE10A and suitable lipophilicity (LogD = 2.2). In PET studies, the binding potential (BPND) of [18F]9 (5.8) to PDE10A in rat brains was significantly higher than that of [18F]5 (4.6). Furthermore, metabolite analysis showed much lower levels of contamination with radiolabeled metabolites of [18F]9 in the brain than those of [18F]5. In conclusion, [18F]9 is a useful PET ligand for PDE10A imaging in brain.},
 pages = {688--698},
 title = {Development of 2-(2-(3-(4-([18F]Fluoromethoxy- d2)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione for Positron-Emission-Tomography Imaging of Phosphodiesterase 10A in the Brain.},
 volume = {62},
 year = {2018}
}