Copper-Mediated Radiosynthesis of [¹⁸F]Rucaparib

Abstract

The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treat <i>BRCA</i>-mutated cancers. Herein, we report two strategies to access the ¹⁸F-isotopologue of rucaparib by applying a copper-mediated nucleophilic ¹⁸F-fluorodeboronation. The most successful approach features an aldehydic boronic ester precursor that is subjected to reductive amination post-¹⁸F-labeling and affords [¹⁸F]rucaparib with an activity yield of 11% ± 3% (<i>n</i> = 3) and a molar activity (<i>A</i>_m) up to 30 GBq/μmol. Preliminary <i>in vitro</i> studies are presented.