Abstract
Radionuclides are distributed nonuniformly in tissue. The present work examined the impact of nonuniformities at the multicellular level on the lethal effects of (210)Po. A three-dimensional (3D) tissue culture model was used wherein V79 cells were labeled with (210)Po-citrate and mixed with unlabeled cells, and multicellular clusters were formed by centrifugation. The labeled cells were located randomly in the cluster to achieve a uniform distribution of radioactivity at the macroscopic level that was nonuniform at the multicellular level. The clusters were maintained at 10.5 degrees C for 72 h to allow alpha-particle decays to accumulate and then dismantled, and the cells were seeded for colony formation. Unlike typical survival curves for alpha particles, two-component exponential dose-response curves were observed for all three labeling conditions. Furthermore, the slopes of the survival curves for 100, 10 and 1% labeling were different. Neither the mean cluster absorbed dose nor a semi-empirical multicellular dosimetry approach could accurately predict the lethal effects of (210)Po-citrate.
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