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

✍ Scribed by Sang Ju Lee; Seung Jun Oh; Dae Yoon Chi; Byoung Se Lee; Jin Sook Ryu; Dae Hyuk Moon

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: French
• Weight: 105 KB
• Volume: 51
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1478

✦ Synopsis

Abstract

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