Synthesis of [18F]-labeled N-3(substituted) thymidine analogues: N-3([18F]fluorobutyl) thymidine ([18F]-FBT) and N-3([18F]fluoropentyl) thymidine ([18F]-FPT) for PET

✍ Scribed by Mian M. Alauddin; Pradip Ghosh; Juri G. Gelovani

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: French
• Weight: 143 KB
• Volume: 49
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1127

✦ Synopsis

Abstract

Syntheses of N‐3(substituted) analogues of thymidine, N‐3([^18^F]fluorobutyl)thymidine ([^18^F]‐FBT) and N‐3([^18^F]fluoropentyl)thymidine ([^18^F]‐FPT) are reported. 1,4‐Butane diol and 1,5 pentane diol were converted to their tosyl derivatives 2 and 3 followed by conversion to benzoate esters 4 and 5, respectively. Protected thymidine 1 was coupled separately with 4 and 5 to produce 6 and 7, which were hydrolyzed to 8 and 9, then converted to their mesylates 10 and 11, respectively. Compounds 10 and 11 were fluorinated with n‐Bu~4~N[^18^F] to produce 12 and 13, which by acid hydrolysis yielded 14 and 15, respectively. The crude products were purified by HPLC to obtain [^18^F]‐FBT and [^18^F]‐FPT. The radiochemical yields were 58–65% decay corrected (d.c.) for 14 and 46–57% (d.c.) for 15 with an average of 56% in three runs per compound. Radiochemical purity was >99% and specific activity was >74 GBq/µmol at the end of synthesis (EOS). The synthesis time was 65–75 min from the end of bombardment (EOB). Copyright © 2006 John Wiley & Sons, Ltd.