@article{oai:repo.qst.go.jp:00048327,
 author = {Yamasaki, Tomoteru and Fujinaga, Masayuki and Shimoda, Yoko and Mori, Wakana and Zhang, Yiding and Wakizaka, Hidekatsu and Ogawa, Masanao and Zhang, Ming-Rong and 山崎 友照 and 藤永 雅之 and 下田 陽子 and 森 若菜 and 張 一鼎 and 脇坂 秀克 and 小川 政直 and 張 明栄},
 issue = {17},
 journal = {Bioorganic & Medicinal Chemistry Letters},
 month = {Jul},
 note = {Cannabinoid receptor type 1 (CB1) is mainly expressed in the brain, as well as being expressed in functional relevant concentrations in various peripheral tissues. 1-(4-Chlorophenyl)-3-(3-(6-(pyrrolidin-1-yl)pyridin-2-yl)phenyl)urea (PSNCBAM-1, 1) was developed as a potent allosteric antagonist for CB1 and its oral administration led to reductions in the appetite and body weight of rats. Several analogs of 1 (compounds 2 and 3) were recently identified through a series of structure-activity relationship studies. Herein, we report the synthesis of radiolabeled analogs of these compounds using [11C]COCl2, and an evaluation of their potential as PET ligands for CB1 imaging using in vitro and in vivo techniques. [11C]2 and [11C]3 were successfully synthesized in two steps using [11C]COCl2. The radiochemical yields of [11C]2 and [11C]3 were 17 ± 8% and 20 ± 9% (decay-corrected to the end of bombardment, based on [11C]CO2). The specific activities of [11C]2 and [11C]3 were 42 ± 36 and 37 ± 13 GBq/μmol, respectively. The results of an in vitro binding assay using brown adipose tissue (BAT) homogenate showed that the binding affinity of 2 for CB1 (KD = 15.3 µM) was much higher than that of 3 (KD = 26.0 µM). PET studies with [11C]2 showed a high uptake of radioactivity in BAT, which decreased considerably in animals pretreated with AM281 (a selective allosteric antagonist for CB1). In conclusion, [11C]2 may be a useful PET ligand for imaging peripheral CB1 in BAT.
2009 Elsevier Ltd. All rights reserved.},
 pages = {4114--4117},
 title = {Radiosynthesis and evaluation of new PET ligands for peripheral cannabinoid receptor type 1 imaging},
 volume = {27},
 year = {2017}
}