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

¹ The Medical and Pharmacological Research Center Foundation, Hakui, Japan
² Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
³ Advanced Technology Platform Research Laboratory, Fujisawa Pharmaceutical Company, Ltd., Tsukuba, Japan
⁴ Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Company, Ltd., Osaka, Japan

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 Arterial blood samples were withdrawn during PET scanning and were analyzed by an automatic well -counter and thin-layer chromatography to determine the time course of authentic ¹⁸F-FK960 activity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 x 10^-7 mol/L (at 3.0 ± 0.6 h after administration) and 4.04 ± 1.29 x 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.

Key Words: N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate • antidementia drug • PET • rhesus monkey • pharmacokinetics

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				H. Takamatsu, A. Noda, Y. Murakami, M. Tatsumi, R. Ichise, and S. Nishimura A PET Study After Treatment with an Anxiety-Provoking Agent, m-Chlorophenyl-Piperazine, in Conscious Rhesus Monkeys J. Nucl. Med., September 1, 2003; 44(9): 1516 - 1521. [Abstract] [Full Text] [PDF]