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

Abstract

Abstract[18F]Fluorothymidine ([18F]FLT) is synthesized with a high radiochemical yield by nucleophilic substitution in protic solvent. In this study, we compared [18F]fluorination yields of [18F]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‐β‐D‐threopentofuranosyl)‐3‐N‐BOC‐thymine as a precursor for [18F]fluorination. [18F]F− was eluted with TBAHCO3 solution after trapping [18F]F− on a PS‐HCO3 cartridge. [18F]fluorination was performed at 100°C for 5–30 min using 20 mg of the precursor. [18F]fluorination and radiochemical yields of [18F]FLT were evaluated by radioTLC. [18F]fluorination yields were dependent on the solvent used. All tertiary alcohol solvents, except 2‐trifluoromethyl‐2‐propanol, showed >85% of [18F]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 [18F]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 [18F]FLT. Copyright © 2008 John Wiley & Sons, Ltd.