68Ga radiolabeling strategies in Pt(iv)-deferoxamine scaffolds for potential theranostic application

Abstract

Since the discovery of cisplatin's anticancer activity and its clinical approval in 1978, substantial efforts have focused on improving its physiological stability and minimizing off-target toxicity. One promising strategy has been the development of Pt(IV) complexes, which act as redox-activated prodrugs with improved pharmacological profiles compared to Pt(II) drugs. In this study, we present the synthesis of three novel Pt(IV) complexes bearing a pendant deferoxamine (DFO) chelator, designed for theranostic application, combining therapeutic activity with radiometal labeling for positron emission tomography (PET) imaging. Platinum-based drugs are still the gold standard therapy for osteosarcoma but the limited utility and the resistance mechanisms indicate an urgent need for new approaches. In vitro studies demonstrated that these complexes are efficiently internalized by osteosarcoma cells and exhibit minimal toxicity toward healthy MDCK.2 kidney cells, indicating a favorable safety profile. Radiolabeling with Gallium-68 was achieved under mild conditions, yielding stable radiotracers in various biological media after 1 h incubation. This study represents one of the first demonstrations of Pt(IV) theranostic agents suitable for PET imaging, enabling future investigations of Pt(IV) biodistribution profiles that go beyond traditional therapeutic evaluations.