Radiometal-Labeled\nPhotoactivatable Pt(IV) Anticancer\nComplex for Theranostic Phototherapy

Abstract

A novel photoactivatable Pt­(IV) diazido anticancer agent, <b>Pt-succ-DFO</b>, bearing a pendant deferoxamine (DFO) siderophore\nfor radiometal chelation, has been synthesized for the study of its <i>in vivo</i> behavior with radionuclide imaging. <b>Pt-succ-DFO</b> complexation of Fe­(III) and Ga­(III) ions yielded new heterobimetallic\ncomplexes that maintain the photoactivation properties and photocytotoxicity\nof the parent Pt complex in human cancer cell lines. Radiolabeled <b>Pt-succ-DFO-⁶⁸Ga</b> (<i>t</i>_1/2 = 68 min, positron emitter) was readily prepared under mild conditions\nand was stable in the dark upon incubation with human serum. PET imaging\nof <b>Pt-succ-DFO-</b>^<b>68</b><b>Ga</b> in healthy mice revealed a promising biodistribution profile with\nrapid renal excretion and limited organ accumulation, implying that\nlittle off-target uptake is expected for this class of agents. Overall,\nthis research provides the first <i>in vivo</i> imaging\nstudy of the whole-body distribution of a photoactivatable Pt­(IV)\nazido anticancer complex and illustrates the potential of radionuclide\nimaging as a tool for the preclinical development of novel light-activated\nagents.