PET as an advanced tool for new drug research and development: Pharmacokinetics study of FK960

Shintaro Nishimura, Ichiro Matsunari, Yoshihiro Murakami, Hiroyuki Takamatsu, Akihiro Noda, Kazuyoshi Yajima, Masamichi Matsudaira, Masatoshi Itoh, Norihisa Tonami, Kinichi Hisada

Research output: Contribution to journalArticlepeer-review


Objectives: Recently, we have used animal and clinical PET for new drug research and development. In such clinical investigation, Good Manufacturing Practice (GMP) and Good Clinical Practice (GCP) regulations are required, and a series of the PET studies of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel antidementia drug, was examined for predicting accurate clinical dose. Methods: (1) Synthesis of [18F]FK960: We developed a rapid synthesis method and an automated apparatus, and constructed the quality control system which is applicable for GMP regulation. (2) Pharmacokinetics study of FK960 in monkey PET: [18F]FK960 was mixed with unlabeled FK960 in saline to administer at dose of 0.1 mg/kg and about 370 MBq for each monkey, and arterial blood samples were withdrawn during the study for metabolite correction. FK960 concentration in the brain was calculated in units of mol/l. (3) Pharmacokinetics study of FK960 in clinical PET: Three male normal volunteers underwent PET imaging for 6 h after oral administration of a mixture of [18F]FK960 (185 MBq) which was synthesized under GMP regulation and unlabeled FK960 (6 mg), and the concentration was also calculated in the similar manner to that of the monkey PET. Results: [18F]FK960 penetrated the blood–brain barrier and perfusion-dependently distributed in the whole brain. In the monkey study, maximal mean concentrations and time of maximal in brain were 1.11×10−7 mol/l (M) and 3.0 h, respectively. On the other hand, the mean concentration in the human brain was highest (2.73×10−7 M) at 1.67 h and was 1.82×10−7 M at 6 h after administration, both of which were considered to be within the range of efficacy in literature. Conclusion: This clinical study is the first GCP PET in Japan and the synthesis of [18F]FK960 succeeded under GMP regulation. In this study, PET can detect the distribution of the new drug candidate in the living body and calculate the brain concentration. The pharmacokinetic study using PET is useful for estimating the clinical dose of the drug candidate and will be a powerful tool for new drug research and development.

Original languageEnglish
Pages (from-to)40-43
Number of pages4
JournalInternational Congress Series
Issue numberC
Publication statusPublished - 2004 Mar 1
Externally publishedYes


  • FK960
  • Pharmacokinetics
  • Positron emission tomography

ASJC Scopus subject areas

  • Medicine(all)


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