Radiolabeled compounds, cis-diammine-(1,1-cyclobutanedicarboxylato)-$\sp{\rm 193m}$Pt(II) (carboplatin) and dipyrrolidinedithiocarbamato-$\sp{212}$Pb(II) (Pb(PDC)$\sb2$) were synthesized in microscale quantities. High performance liquid chromatography (HPLC) techniques were employed as both a synthetic tool and mode of product analysis. The specific activities of the purified radiochemicals were in the gigabecquerel per mg range. This was adequate for radiobiological experiments and is several orders of magnitude higher than that required for tracer studies. The radionuclide $\sp{\rm 193m}$Pt with 4.3 day half-life emits numerous low energy Auger electrons by virtue of its 3-step isomeric decay essentially by internal conversion. The yields and energies of the electrons were calculated using Monte Carlo methods. This radionuclide was produced by the $\sp{192}$Pt(n,$\gamma)\sp{\rm 193m}$Pt reaction. Other avenues of production, $\sp{192}$Os($\alpha$,3n)$\sp{\rm 193m}$Pt, were also considered. The $\beta$ emitting $\sp{212}$Pb, which decays to $\alpha$ particle emitting daughters, was isolated from a $\sp{226}$Ra generator. The clonogenic survival of Chinese hamster V79 cells was investigated using both radiolabeled and nonradiolabeled forms of the compounds. The effects of the two types of ionizing radiation (Auger electrons and $\alpha$ particles), kinetics of cellular uptake and retention, and subcellular distribution of these compounds were studied. The dosimetry calculations were performed using the radiation spectra, biokinetics, and Medical Internal Radiation Dose (MIRD) formalism. The mean lethal values of dose (D$\sb{37}$) for the radiolabeled carboplatin and $\sp{212}$Pb(PDC)$\sb2$ were 0.453 grays and 0.85 grays, respectively. The values of relative biological effectiveness (RBE) were estimated to be about 8.8 for radiolabeled carboplatin and 4.6 (2.4 with recoil of the daughter nuclei included) for radiolabeled $\sp{212}$Pb(PDC)$\sb2.$ The results confirm the inadequacy of the current methods of dose calculation (MIRD) and International Commission on Radiation Units and Measurements (ICRU) and point to the potential usefulness of $\sp{\rm 193m}$Pt-carboplatin in chemo-Auger combination therapy of cancer.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:dissertations-4771 |
| Date | 01 January 1993 |
| Creators | Azure, Michael Thomas |
| 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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