Synthesis of 18 F 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
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.633

The present study demonstrated the synthesis and in vivo study of 18 F‐labeled N ‐(4‐acetyl‐1‐piperazinyl)‐ p ‐fluorobenzamide (FK960) which is a novel anti‐dementia drug candidate. [ 18 F]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 [ 18 F]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 [ 18 F]FK960 was injected into 3 conscious monkeys (100–120 MBq/kg body weight), and distribution images and pharmacokinetic data for [ 18 F]FK960 showed similar uptake in different brain regions and 3‐fold higher levels of [ 18 F]FK960 in blood relative to brain. Copyright © 2002 John Wiley & Sons, Ltd.