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

Cu-mediated radiofluorination is a versatile tool for the preparation of F-18-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 F-18-labeling yields despite use of lower precursor amounts. Impressively, application of 2.5 mu mol aryl boronic acids was sufficient to achieve F-18-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-[F-18]FPhe and 6-[F-18]FDOPA were prepared in activity yields of 23 +/- 1 % and 30 +/- 3 % using only 2.5 mu mol of the corresponding boronic acid or trimethylstannyl precursor.

Automated summary

In this study, a series of complexes were systematically evaluated and several generally applicable mediators were identified for highly efficient radiofluorination. The utilization of these mediators significantly improved the labeling yields, even with lower precursor amounts. The practicality of the novel mediators was demonstrated by the efficient production of five PET tracers and transfer of the method to an automated radiosynthesis module.