The metastable radionuclide Pt-195m decays predominantly by internal conversion (IC) with a half-life of 4 days. The vacancies created in the inner atomic shells by the primary IC decay modes result in copious emission of low energy Auger electrons. The biological effects of these electrons, which have ranges of subcellular dimensions, are of interest to basic and applied radiation biophysics. Using radiolabeled platinum complexes which bind to DNA, one can examine the effect of Pt-195m Auger cascades close to the DNA. Trans-Pt-195m (trans-dichlorodiammineplatinum (II); specific activity 0.5 mCi/mg), a DNA-binding compound, has been synthesized and its effect on the survival of Chinese hamster V79 cells determined. The cellular uptake of Pt-195m reaches a plateau in 3-4 hours and varies nonlinearly with extracellular activity concentration. Following an 18 hour incubation, 75% of the cellular radioactivity is found in the cytoplasm, and 25% in the nucleus. About 42% of the activity in the nucleus is DNA-bound. The activity is eliminated from the cell, postincubation, with a 24 hour half-life. Cell survival data, when corrected for the chemical toxicity of the unlabeled trans-Pt, give a survival curve typical of densely ionizing radiation of high linear energy transfer such as alpha particles. The mean lethal cellular uptake of radioactivity is 0.032 $\pm$ 0.003 pCi/cell at 37% survival. Theoretical calculations of the Pt-195m Auger electron spectrum using Monte Carlo methods indicate about 30 Auger electrons are expected per decay. Dosimetric considerations give a value of 4.8 for the relative biological effectiveness of Pt-195m compared to 250 kVp x-rays. Theoretical Monte Carlo calculations imply that the density of chemical species produced by Auger electrons in liquid water in the immediate vicinity of a Pt-195m decay site is comparable to the density along the track of a 4 MeV alpha particle. This explains qualitatively the efficacy of Pt-195m in causing biological effects. Potential therapeutic applications of radioplatinum complexes are noted. This work is supported in part by U.S.P.H.S. Grants CA-32877 and CA-15523.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:dissertations-5512 |
| Date | 01 January 1987 |
| Creators | Howell, Roger Wells |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Language | English |
| Detected Language | English |
| Type | text |
| Source | Doctoral Dissertations Available from Proquest |
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