@article{oai:repo.qst.go.jp:00048389,
 author = {Kawamura, Kazunori and Fujinaga, Masayuki and Shimoda, Yoko and Yamasaki, Tomoteru and Zhang, Yiding and Hatori, Akiko and Xie, Lin and Wakizaka, Hidekatsu and Kumata, Katsushi and Ohkubo, Takayuki and Kurihara, Yusuke and Ogawa, Masanao and Nengaki, Nobuki and Zhang, Ming-Rong and 河村 和紀 and 藤永 雅之 and 下田 陽子 and 山崎 友照 and 張 一鼎 and 羽鳥 晶子 and 謝 琳 and 脇坂 秀克 and 熊田 勝志 and 大久保 崇之 and 栗原 雄祐 and 小川 政直 and 念垣 信樹 and 張 明栄},
 journal = {Nuclear Medicine and Biology},
 month = {Jun},
 note = {Introduction: `The growth hormone secretagogue receptor 1a (GHS-R1a) is the orphan G-protein-coupled receptor,
and its endogenous ligand is ghrelin. GHS-R1a contributes to regulation of glucose homeostasis,memory and learning,
food addiction, and neuroprotection. Several PET tracers for GHS-R1a have been developed, but none have been reported
to be clinically applicable to GHS-R1a imaging. In this study, we developed three new PET tracers for GHSR1a:
18F-labeled 6-(4-chlorophenyl)-3-((1-(2-fluoroethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one
(1), 11C-labeled 6-(4-chlorophenyl)-3-((1-(2-methoxyethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-
one (2), and 11C-labeled (S)-(4-(1H-indole-6-carbonyl)-3-methylpiperazin-1-yl)(4′-methoxy-[1,1′-biphenyl]-4-
yl)methanone (3).
Methods: [18F]1was synthesized by the 18F-fluoroethylation; [11C]2 or [11C]3 was synthesized by the 11C-methylation.
Biodistribution studies and PET studies were conducted in mice.
Results:Wesuccessfully radiosynthesized [18F]1, [11C]2, and[11C]3 with appropriate radioactivity for the animal study.
In the ex vivo biodistribution study, 60 min following injection, the radioactivity level of [18F]1 was relatively high in
the small intestine, that of [11C]2was high in the liver, and that of [11C]3was high in the pancreas. The radioactivity
levels of the three PET tracerswere relatively low in the brain. Under pretreatmentwith YIL781 (a selective and high
affinity antagonist for GHS-R1a), the pancreas radioactivity level at 30min following [11C]3 injectionwas significantly
reduced to 55% of control, but the radioactivity in the brain was not changed. In the PET study under control conditions,
high radioactivity levels in the liver and pancreas were observed following [11C]3 injection. With YIL781 pretreatment,
the accumulated radioactivity in the pancreas 15–60 min after [11C]3 injection was significantly
decreased to 78% of control.
Conclusion: [11C]3 exhibited relatively high uptake and in vivo specific binding to GHS-R1a in the mouse pancreas.
[11C]3 may be a useful PET tracers for in vivo imaging of GHS-R1a in the pancreas.},
 pages = {49--56},
 title = {Developing new PET tracers to image the growth hormone secretagogue receptor 1a (GHS-R1a)},
 volume = {52},
 year = {2017}
}