Next Generation Copper Mediators for the Efficient Production of <sup>18</sup>F‐Labeled Aromatics
Chris Hoffmann, Niklas Kolks, Daniel Smets, Alexander Haseloer, Benedikt Gröner, Elizaveta A. Urusova, Heike Endepols, Felix Neumaier, Uwe Ruschewitz, Axel Klein, Bernd Neumaier, Boris D. Zlatopolskiy
Abstract
Abstract 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 n BuOH/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.