Measurement of Brain Concentration of FK960 for Development of a Novel Antidementia Drug: A PET Study in Conscious Rhesus Monkeys

Journal of Nuclear Medicine

Akihiro Noda¹  Mitsuyoshi Tatsumi¹  Rikiya Ichise¹  Shintaro Nishimura¹  Hiroyuki Takamatsu¹  Kazuyoshi Yajima¹  Yoshihiro Murakami¹ 

关键词: N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate;    antidementia drug;    PET;    rhesus monkey;    pharmacokinetics;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

This study used PET to measure the time course of the brain concentration of 18F-labeled N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960), a novel antidementia drug, after oral administration to conscious rhesus monkeys. Methods: Three young-adult male rhesus monkeys were tested. FK960 (0.1 mg/kg) containing about 370 MBq of 18F-FK960 was administered orally to each monkey. Dynamic PET images were acquired for 4 h from 5 min after the administration. Arterial blood samples were withdrawn during PET scanning and were analyzed by an automatic well γ-counter and thin-layer chromatography to determine the time course of authentic 18F-FK960 activity concentration in plasma. FK960 concentrations in brain and plasma were calculated in units of mol/L using the specific activity of FK960 preparations. Results: 18F-FK960 penetrated the blood–brain barrier and underwent perfusion-dependent distribution in the entire brain. Maximal concentrations in the brain and plasma were 1.11 ± 0.30 × 10−7 mol/L (at 3.0 ± 0.6 h after administration) and 4.04 ± 1.29 × 10−7 mol/L (at 2.0 ± 1.1 h after administration), respectively. Conclusion: We succeeded in measuring the FK960 concentration in the brains of conscious monkeys and in plasma after oral administration at a dose of 0.1 mg/kg. The results suggested that this method can measure the FK960 concentration in the human brain, and a potential use of the PET technique in drug development was demonstrated.

【 授权许可】

Unknown