Synthesis of 18F labelled FK960, a candidate anti-dementia drug, and PET studies in conscious monkeys

• Published in: Journal of labelled compounds & radiopharmaceuticals 2002-12, Vol.45 (14), p.1219-1228
• Main Authors: Murakami, Yoshihiro, Nishimura, Shintaro, Noda, Akihiro, Harada, Norihiro, Tsukada, Hideo
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chemistry; Contrast media. Radiopharmaceuticals; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Medical sciences; Organic chemistry; Pharmacology. Drug treatments; Preparations and properties
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.633

The present study demonstrated the synthesis and in vivo study of 18F‐labeled N‐(4‐acetyl‐1‐piperazinyl)‐p‐fluorobenzamide (FK960) which is a novel anti‐dementia drug candidate. [18F]FK960 was prepared by a one‐pot, three reaction sequence, using nucleophilic fluorination, with an automated synthetic apparatus using either ethyl‐4‐trimethylammonium triflate (1a) or ethyl‐4‐nitrobenzoate (1b) as the precursor for labeling. Though 1a gave a higher yield, the specific activity was 50–100 fold higher with 1b. The radiochemical yield of [18F]FK960 was 7–15% (EOB) and the specific activity ranged from 2.0–60.2 GBq/μmol depending on the amount of F‐18 used. The synthesis time was 2.2–2.9 h. The obtained [18F]FK960 was injected into 3 conscious monkeys (100–120 MBq/kg body weight), and distribution images and pharmacokinetic data for [18F]FK960 showed similar uptake in different brain regions and 3‐fold higher levels of [18F]FK960 in blood relative to brain. Copyright © 2002 John Wiley & Sons, Ltd.