Next Generation Copper Mediators for the Efficient Production of ¹⁸ F-Labeled Aromatics

Cu-mediated radiofluorination is a versatile tool for the preparation of ¹⁸ F-labeled (hetero)aromatics. In this work, we systematically evaluated a series of complexes and identified several generally applicable mediators for highly efficient radiofluorination of aryl boronic and stannyl substrates. Utilization of these mediators in nBuOH/DMI or DMI significantly improved ¹⁸ F-labeling yields despite use of lower precursor amounts. Impressively, application of 2.5 μmol aryl boronic acids was sufficient to achieve ¹⁸ F-labeling yields of up to 75 %. The practicality of the novel mediators was demonstrated by efficient production of five PET-tracers and transfer of the method to an automated radiosynthesis module. In addition, (S)-3-[¹⁸ F]FPhe and 6-[¹⁸ F]FDOPA were prepared in activity yields of 23±1 % and 30±3 % using only 2.5 μmol of the corresponding boronic acid or trimethylstannyl precursor.