Development of Novel (191)Pt-Labeled Hoechst33258: (191)Pt Is More Suitable than (111)In for Targeting DNA

[Image: see text] This study aims to establish new labeling methods for no-carrier-added radio-Pt ((191)Pt) and to evaluate the in vitro properties of (191)Pt-labeled agents compared with those of agents labeled with the common emitter (111)In. (191)Pt was complexed with the DNA-targeting dye Hoechst33258 via diethylenetriaminepentaacetic acid (DTPA) or the sulfur-containing amino acid cysteine (Cys). The intranuclear fractions of (191)Pt- and (111)In-labeled Hoechst33258 were comparable, indicating that the labeling for (191)Pt via DTPA or Cys and the labeling for (111)In via DTPA worked equally well. (191)Pt showed a DNA-binding/cellular uptake ratio of more than 1 order of magnitude greater than that of (111)In. [(191)Pt]Pt-Hoechst33258 labeled via Cys showed a higher cellular uptake than that labeled via DTPA, resulting in a very high DNA-binding fraction of [(191)Pt]Pt-Cys-Hoechst33258 and extensive DNA damage. Our labeling methods of radio-Pt, especially via Cys, promote the development of radio-Pt-based agents for use in Auger electron therapy targeting DNA.