Lognormal Distribution of Cellular Uptake of Radioactivity: Monte Carlo Simulation of Irradiation and Cell Killing in 3-Dimensional Populations in Carbon Scaffolds

Abstract

The biologic response of tissue exposed to radiation emitted by internal radioactivity is often correlated with the mean absorbed dose to a tissue element. However, studies show that even when the macroscopic absorbed dose to the tissue element is constant, the response of the cell population within the tissue element can vary significantly, depending on the distribution of radioactivity at the cellular and multicellular levels. These variations are believed to be the consequence of nonuniform distributions of activity among the cells or subcellular compartments that comprise the tissue element. Furthermore, the self-dose received by a cell containing radioactivity can be more radiotoxic than the cross-dose from neighboring cells. To study how the nonuniformity of activity among cells can affect the dose response, a 3-dimensional model of cells in a heterogeneous carbon scaffold was used to assess response. A theoretic model of a 3-dimensional cell culture was constructed, and Monte Carlo radiation transport was performed to assess self- and cross-doses for each cell nucleus in a population of 10(6) cells. On the basis of these individual doses and on empiric models of radiation-induced cell death (i.e., reproductive failure), survival curves were simulated with different electron energies and activity distributions among the cells. Nonuniformity of cell activities are responsible for nonuniformity of the dose at the cellular level, which in turn causes a change in the surviving fraction of the cell population from that expected on the basis of uniform activity and dose. The macroscopic dose received by a tissue cannot be used to anticipate its biologic response. The dose distribution among individual cells, because of both their nonuniform activity and geometric environment, is an important factor in determining biologic response of the tissue at the macroscopic level.