Radiometal-Labeled Photoactivatable Pt(IV) Anticancer Complex for Theranostic Phototherapy
Cinzia Imberti, Jamie Guan-Tai Lok, James P. C. Coverdale, Oliver W. L. Carter, M. Fry, Miles Postings, Jana Kim, George Firth, Philip J. Blower, Peter J. Sadler
Abstract
High Resolution Image Download MS PowerPoint Slide A novel photoactivatable Pt(IV) diazido anticancer agent, Pt-succ-DFO, bearing a pendant deferoxamine (DFO) siderophore for radiometal chelation, has been synthesized for the study of its in vivo behavior with radionuclide imaging. Pt-succ-DFO complexation of Fe(III) and Ga(III) ions yielded new heterobimetallic complexes that maintain the photoactivation properties and photocytotoxicity of the parent Pt complex in human cancer cell lines. Radiolabeled Pt-succ-DFO- 68 Ga ( t 1/2 = 68 min, positron emitter) was readily prepared under mild conditions and was stable in the dark upon incubation with human serum. PET imaging of Pt-succ-DFO- 68 Ga in healthy mice revealed a promising biodistribution profile with rapid renal excretion and limited organ accumulation, implying that little off-target uptake is expected for this class of agents. Overall, this research provides the first in vivo imaging study of the whole-body distribution of a photoactivatable Pt(IV) azido anticancer complex and illustrates the potential of radionuclide imaging as a tool for the preclinical development of novel light-activated agents.