RADIOTOXICITY OF PLATINUM-195M-LABELED TRANS-PLATINUM(II) IN MAMMALIAN-CELLS

The chemotoxicity and radiotoxicity of trans-dichloro-diammineplatinum (II) labeled with Pt-195m (trans-Pt-195m) are investigated to ascerta in the potential of radioplatinum coordination complexes as antineopla stic agents. Platinum-195m, with a half-life of about 4 days, is a pro lific emitter of low-energy Auger electrons because of the high probab ility of internal conversion in its isomeric transitions. The kinetics of cellular uptake and retention after incubation and the radiotoxici ty of this Auger electron emitter in the form of trans-Pt-195m is inve stigated using cells of the Chinese hamster V79 cell line. The cellula r uptake of Pt-195m reaches a plateau in about 3 to 5 h of incubation and varies nonlinearly with the extracellular concentration of radioac tivity. The radioactivity is eliminated from the cells after incubatio n with an effective half-life of 24 h. Cell survival data, when correc ted for the chemical toxicity of nonradiolabeled trans-platinum, give a cell survival curve typical for radiations with high linear energy t ransfer. At 37% survival, the mean lethal cellular uptake is about 1.0 mBq/cell. Dosimetric considerations, based on subcellular distributio n of the radionuclide, yield a value of 4.8 for the relative biologica l effectiveness when compared with 250 kVp X rays. Theoretical Monte C arlo track-structure calculations indicate that the density of radical species produced in liquid water in the immediate vicinity of a Pt-19 5m decay site is substantially greater than the density of species alo ng the track of a 5.3 MeV alpha particle. This explains qualitatively the efficacy of Pt-195m in causing high-LET radiation type biological effects. The extreme radiotoxicity of intranuclearly localized Pt-195m , in conjunction with the proclivity of platinum chemotherapy agents t o bind to DNA in the cell nucleus, suggests that the combination of ch emical effects and the effects of Auger electrons that can be obtained with radio-platinum coordination complexes may have potential in the treatment of cancer.