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

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.