@article{oai:repo.qst.go.jp:00080546,
 author = {Zhang, Xiaofei and Zhang, Yiding and Chen, Zhen and Shao, Tuo and Van, Richard and Kumata, Katsushi and Deng, Xiaoyun and Fu, Hualong and Yamasaki, Tomoteru and Rong, Jian and Kuan, Hu and Hatori, Akiko and Xie, Lin and Yu, Qingzhen and Ye, Weijian and Xu, Hao and J. Sheffler, Douglas and D. P. Cosford, Nicholas and Shao, Yihan and Tang, Pingping and Lu, Wang and Ming-Rong, Zhang and Liang, Huan and Zhang, Yiding and Katsushi, Kumata and Tomoteru, Yamasaki and Kuan, Hu and Akiko, Hatori and Lin, Xie and Lu, Wang and Zhang, Ming-Rong and Liang, Huan},
 issue = {24},
 journal = {Theranostics},
 month = {Sep},
 note = {Selective modulation of metabotropic glutamate receptor 2 (mGlu2) represents a novel therapeutic approach for treating brain disorders, including schizophrenia, depression, Parkinson’s disease (PD), Alzheimer’s disease (AD), drug abuse and addiction. Imaging mGlu2 using positron emission tomography (PET) would allow in vivo quantification under physiological and pathological conditions and facilitate drug discovery by enabling target engagement studies. However, to date, few successful efforts have been disclosed to visualize mGlu2 in vivo, indicating an unmet and urgent clinical need. Herein we report the synthesis and preclinical evaluation of a focused library of mGlu2 modulators amenable for radiolabeling. The promising candidate 4-(2,4-difluorophenyl)-7-((2-methoxypyridin -4-yl)methyl)-5,6,7,8-tetrahydro-1,7-naphthyridine-2-carboxamide (21b), exhibited high potency and excellent subtype selectivity, which was then evaluated by in vitro autoradiography and in vivo PET imaging studies after labeling with carbon-11. Ligand [11C]21b (also known as [11C]MG2-1904) demonstrated high brain uptake and excellent in vitro/in vivo specific binding towards mGlu2 with high metabolic stability in the brain. As proof-of-concept, our preliminary work demonstrated a successful example of visualizing mGlu2 in vivo derived from negative allosteric modulators (NAMs), which represents a promising chemotype for further development and optimization aimed for clinical translation.},
 pages = {11178--11196},
 title = {Synthesis and Preliminary Studies of 11C-labeled Tetrahydro-1,7-Naphthyridine-2-Carboxamides for PET Imaging of Metabotropic Glutamate Receptor 2},
 volume = {10},
 year = {2020}
}