19F NMR Allows to Investigate the Fate of Platinum(IV) Prodrugs in Physiological Conditions.

Pt(IV) prodrugs can overcome resistance and side effects of conventional Pt(II) anticancer therapies. By 19 F-labeling of a Pt(IV) prodrug (Pt-FBA, FBA = p -fluorobenzoate), the activation under physiological conditions could be investigated. It is found that, unlike single-electron reductants, multi-electron agents can efficiently promote the two electrons reduction of Pt(IV) to Pt(II). Moreover, the activation of Pt-FBA in cell lysate is highly dependent upon the type of cancer cells. When administered to E. coli , Pt-FBA is reduced intracellularly and free FBA can shuttle out of the cell. Interestingly, the reduction rate greatly increases by inducing metallothionein overexpression and is lowered by addition of Zn(II) ions. Finally, when injected into mice, Pt-FBA undergoes fast reduction in the bloodstream accompanied by metabolic degradation of FBA; nevertheless, unreduced Pt-FBA can accumulate to detectable levels in liver and kidneys. The proposed 19 F-NMR approach has the advantage of avoiding the interference of all background signals.