In Vivo Imaging of a Photoactivatable Platinum Prodrug by Metal-Centered Radiolabeling

The in vivo fate of metal-based photoactivatable prodrugs is often unknown or inferred from structurally modified analogues rather than the drug candidates themselves, which may lack suitable spectroscopic reporters. New methods are needed to reveal authentic biological behavior. We report the multistep radiosynthesis of a photoactivatable platinum(IV) prodrug and new insights into its biomolecular properties from single-photon emission computed tomography imaging using (metastable) platinum-195m. Metal-centered radiolabeling preserves both the chemical identity and photoreactivity of the non-radioactive prodrug and enables direct radioanalytical tracking in biological media and in vivo. Whole-body imaging in healthy and tumor-bearing mice revealed rapid renal clearance of the drug, with unexpected and persistent accumulation in the bladder wall, a behavior not observed for cisplatin or structurally-modified analogues. These results demonstrate how metal-centered radiolabeling enables direct interrogation of the in vivo fate of metal-based photoactivatable drug candidates and reveals biological behavior information that is inaccessible using indirect labeling strategies.