Simplified Labeling Approach for Synthesizing 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT)

Abstract

[¹⁸F]FLT (3′-deoxy-3′-[¹⁸F]fluorothymidine) turned out to be a tracer particularly suitable for PET imaging of tumor proliferation because of lacking degradation in vivo. To facilitate clinical studies with [¹⁸F]FLT, we investigated two new easily accessible precursors, 2,3′-anhydrothymidine (AThy) and 5′-O-(4,4′-dimethoxytriphenylmethyl)-2,3′-anhydrothymidine (DMTThy), using a common approach for introducing the label with nucleophilic [¹⁸F]fluoride. Radiochemical yields were determined in dependence on substrate concentration, reaction time and temperature. In the case of AThy (10 mg), best FLT yields were 5.3%±1.2 (130 °C, 30 min). Labeling of DMTThy (10 mg) gave 14.3%±3.3 at 160 °C within 10 minutes. Starting with an aqueous solution of 20 GBq [¹⁸F]fluoride the new method allows to produce 1.3 GBq [¹⁸F]FLT within 90 minutes ready for intravenous injection. The new labeling procedures allow [¹⁸F]FLT synthesis without lengthy preparation of the precursor and with high reproducibility mandatory for clinical application.