Radiosynthesis and in vivo evaluation of 11 C-labeled BMS-193885 and its desmethyl analog as PET tracers for neuropeptide Y1 receptors.

Autor: Kawamura K; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan. kawamura.kazunori@qst.go.jp., Mori W; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan., Fujinaga M; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan., Yamasaki T; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan., Zhang Y; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan., Wakizaka H; Department of Medical Physics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan., Hatori A; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan., Xie L; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan., Kumata K; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan., Ohkubo T; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.; SHI Accelerator Service Ltd, Tokyo, 141-0032, Japan., Kurihara Y; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.; SHI Accelerator Service Ltd, Tokyo, 141-0032, Japan., Ogawa M; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.; SHI Accelerator Service Ltd, Tokyo, 141-0032, Japan., Nengaki N; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.; SHI Accelerator Service Ltd, Tokyo, 141-0032, Japan., Zhang MR; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Jazyk: angličtina
Zdroj: EJNMMI radiopharmacy and chemistry [EJNMMI Radiopharm Chem] 2019 Feb 18; Vol. 4 (1), pp. 4. Date of Electronic Publication: 2019 Feb 18.
DOI: 10.1186/s41181-019-0056-5
Abstrakt: 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 11 C-labeled BMS-193885 ([ 11 C]1) and its desmethyl analog ([ 11 C]2) for potential use as two new positron emission tomography (PET) tracers.
Results: [ 11 C]1 was synthesized from [ 11 C]methyl iodide using 2. [ 11 C]2 was synthesized from [ 11 C]phosgene using its aniline and amine derivatives. The mean ± S.D. decay-corrected radiochemical yields of [ 11 C]1 and [ 11 C]2 from 11 CO 2 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 [ 11 C]1 were significantly reduced by pretreatment with 1 (10 mg/kg), and levels of [ 11 C]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, [ 11 C]1 and [ 11 C]2 were rapidly metabolized within 30 min post-injection, and [ 11 C]1 was mainly metabolized into unlabeled 2 and radiolabeled components.
Conclusion: [ 11 C]1 and [ 11 C]2 were successfully synthesized with sufficient amount of radioactivity and high quality for use in vivo. Our study of [ 11 C]1 and its desmethyl analog [ 11 C]2 was useful in that it helped to elucidate the in vivo characteristics of 1.
Databáze: MEDLINE
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