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

摘要

Syntheses of N-3(substituted) analogues of thymidine, N-3([ 18F]fluorobutyl)thymidine ([18F]-FBT) and N-3([ 18F]fluoropentyl)thymidine ([18F]-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-Bu4N[ 18F] to produce 12 and 13, which by acid hydrolysis yielded 14 and 15, respectively. The crude products were purified by HPLC to obtain [ 18F]-FBT and [18F]-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.