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This study used PET to measure the time course of the brain concentration of (18)F-labeled N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960), a novel antidementia drug, after oral administration to conscious rhesus monkeys. Three young-adult male rhesus monkeys were tested. FK960 (0.1 mg/kg) containing about 370 MBq of (18)F-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 Arterial blood samples were withdrawn during PET scanning and were analyzed by an automatic well gamma-counter and thin-layer chromatography to determine the time course of authentic (18)F-FK960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. (18)F-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. 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.

Citation

Akihiro Noda, Hiroyuki Takamatsu, Yoshihiro Murakami, Kazuyoshi Yajima, Mitsuyoshi Tatsumi, Rikiya Ichise, Shintaro Nishimura. Measurement of brain concentration of FK960 for development of a novel antidementia drug: a PET study in conscious rhesus monkeys. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2003 Jan;44(1):105-8

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PMID: 12515883

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