Exploring Solvent Effects In The Radiosynthesis Of F-18-Labeled Thymidine Analogues Toward Clinical Translation For Positron Emission Tomography Imaging

Thymidine analogues, 5-substituted 2'-deoxy-2'-[F-18]fluoro-arabinofuranosyluracil derivatives, are promising positron emission tomography (PET) tracers being evaluated for noninvasive imaging of cancer cell proliferation and/or reporter gene expression. We report the radiosynthesis of 2'-deoxy-2'-[F-18]fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ([F-18]FMAU) and other 2'-deoxy-2'-[F-18]fluoro-5-substituted-1-beta-D-arabinofuranosyluracil analogues using 1,4-dioxane to replace the currently used 1,2dichloroethane. Compared to 1,2-dichloroethane, 1,4-dioxane is analyzed as a better solvent in terms of radiochemical yield and toxicity concern. The use of a less toxic solvent allows for the translation of the improved approach to clinical production. The new radiolabeling method can be applied to an extensive range of uses for F-18-labeling of other nucleoside analogues.