@article{oai:repo.qst.go.jp:00073424,
 author = {Kawamura, Kazunori and Mori, Wakana and Fujinaga, Masayuki and Yamasaki, Tomoteru and Zhang, Yiding and Wakizaka, Hidekatsu and Hatori, Akiko and Xie, Lin and Kumata, Katsushi and Ohkubo, Takayuki and Kurihara, Yusuke and Ogawa, Masanao and Nengaki, Nobuki and Ming-Rong, Zhang and Kawamura, Kazunori and Mori, Wakana and Fujinaga, Masayuki and Yamasaki, Tomoteru and Zhang, Yiding and Wakizaka, Hidekatsu and Hatori, Akiko and Xie, Lin and Kumata, Katsushi and Ohkubo, Takayuki and Kurihara, Yusuke and Ogawa, Masanao and Nengaki, Nobuki and Ming-Rong, Zhang},
 issue = {4},
 journal = {EJNMMI Radiopharmacy and Chemistry},
 month = {Feb},
 note = {Background: Neuropeptide Y (NPY) has been implicated in a wide variety of
physiological processes, including feeding, learning, memory, emotion, cardiovascular
homeostasis, hormone secretion, and circadian rhythms. NPY Yl receptor (NPY Y1-R) is
the most widely studied NPY receptor, and is involved in many of these processes.
BMS-193885 (1) was previously developed as a potent and selective NPY Y1-R
antagonist, which has good systemic bioavailability and brain penetration. To evaluate
the characteristics of 1 in vivo, we developed 11C-labeled BMS-193885 ([11C]1) and its
desmethyl analog ([11C]2) for potential use as two new positron emission tomography
(PET) tracers.
Results: [11C]1 was synthesized from [11C]methyl iodide using 2. [11C]2 was
synthesized from [11C]phosgene using its aniline and amine derivatives. The mean
± S.D. decay-corrected radiochemical yields of [11C]1 and [11C]2 from 11CO2 at the
end of radionuclide production were 23 ± 3.2% (n = 6) and 24 ± 1.5% (n = 4),
respectively. In biodistribution on mice, radioactivity levels for both tracers were
relatively high in the kidney, small intestine, and liver at 60 min post-injection. The
radioactivity levels in the kidney, lung, and spleen of mice at 30 min post-injection
with [11C]1 were significantly reduced by pretreatment with 1 (10 mg/kg), and levels of
[11C]1 in the brain of mice were significantly increased by pretreatment with the
P-glycoprotein and breast cancer resistance protein inhibitor elacridar (10 mg/kg).
In metabolite analysis using mouse plasma, [11C]1 and [11C]2 were rapidly
metabolized within 30 min post-injection, and [11C]1 was mainly metabolized
into unlabeled 2 and radiolabeled components.
Conclusion: [11C]1 and [11C]2 were successfully synthesized with sufficient amount
of radioactivity and high quality for use in vivo. Our study of [11C]1 and its desmethyl
analog [11C]2 was useful in that it helped to elucidate the in vivo characteristics of 1.
Keywords: Carbon-11, Positron emission tomography, Neuropeptide Y1 receptor,
BMS-193885},
 title = {Radiosynthesis and in vivo evaluation of 11C-labeled BMS-193885 and its desmethyl analog as PET tracers for neuropeptide Y1 receptors},
 volume = {4},
 year = {2019}
}