No-carrier added synthesis of ¹⁸F-labelled nucleosides using Stille cross-coupling reactions with 4-[¹⁸F]fluoroiodobenzene

The radiosyntheses of 5-(4´-[¹⁸F]fluorophenyl)-uridine [¹⁸F]-11 and 5-(4´-[¹⁸F]fluorophenyl)-2´-deoxy-uridine [¹⁸F]-12 are described. The 5-(4´-[¹⁸F]fluoro-phenyl)-substituted nucleosides were prepared via a Stille cross-coupling reaction with 4-[¹⁸F]fluoroiodobenzene followed by basic hydrolysis using 1 M potassium hydroxide. The Stille cross-coupling rreaction was optimized by screening various palladium complexes, additives and solvents. By using optimized labelling conditions (Pd₂(dba)₃/CuI/AsPh₃ in DMF/dioxane (1:1), 20 min at 65 °C), 550 MBq of [4-¹⁸F]fluoroiodobenzene could be converted into 120 MBq (33 %, decay-corrected) of 5-(4´-[¹⁸F]fluorophenyl)-2´-deoxy-uridine [¹⁸F]-12 within 40 min, including HPLC purification.