Comparison of synthesis yields of 3′-deoxy-3′-[18F]fluorothymidine by nucleophilic fluorination in various alcohol solvents

[F-18]Fluorothymidine ([F-18]FLT) is synthesized with a high radiochemical yield by nucleophilic substitution in protic solvent. In this study, we compared [F-18]fluorination yields of [F-18]fluorothymidine ([18F]FLT) in various alcohol solvents: 3,3-dimethyl-1-butanol, 2-trifluoromethyl-2-propanol, t-BuOH (2-methyl-2-propanol), t-amyl alcohol (2-methyl-2-butanol), thexyl alcohol (2,3-dimethyl-2-butanol) and 3,3-dimethyl-2-butanol. We used 5'-O-DMTr-2'-deoxy-3'-O-nosyl-p-beta-threopentofuranosyl)-3-N-BOC-thymine as a precursor for [F-18]fluorination. [F-18]F- was eluted with TBAHCO(3) solution after trapping [F-18]F- on a PS-HCO3 cartridge. [F-18]fluorination was performed at 100 degrees C for 5-30min using 20mg of the precursor. [F-18]fluorination and radiochemical yields of [F-18]FLT were evaluated by radio TLC. [F-18]fluorination yields were dependent on the solvent used. All tertiary alcohol solvents, except 2-trifluoromethyl-2-propanol, showed >85% of [F-18]fluorination yields, whereas primary and secondary alcohols showed 26.3-71.8%. The highest yield of 94.1 +/- 4.4% was obtained with thexyl alcohol after [F-18]fluorination for 5 min. Automated synthesis with t-amyl alcohol resulted in high synthetic yields of 64.6 +/- 6.1% after high-performance liquid chromatography purification (n=43). The use of tertiary alcohol as a solvent provides high radiochemical yields of [F-18]FLT.