Monte Carlo simulation of irradiation and killing in three-dimensional cell populations with lognormal cellular uptake of radioactivity

Purpose: The biological response of tissue exposed to radiations emitted by internal radioactivity is often correlated with the mean absorbed dose to a tissue element. However, experimental studies show that even when the mean 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. The present work develops theoretical models to simulate these observations. Materials and methods: Two theoretical models were created to simulate experimental three-dimensional cell culture models with homogeneous and inhomogeneous tissue environments. The cells were assigned activities according to lognormal distributions of an alpha particle emitter or a monoenergetic electron emitter. Absorbed doses to the cell nuclei were assessed with point-kernel geometric-factor and Electron Gamma Shower version nrc (EGSnrc) Monte Carlo radiation transport simulations, respectively. The self- and cross-dose to individual cell nuclei were calculated and a Monte Carlo method was used to determine their fate. Survival curves were produced after tallying the live and dead cells. Results: Both percent cells labeled and breadth of lognormal distribution affected the dose distribution at the cellular level, which in turn, influenced the shape of the cell survival curves. Conclusions: Multicellular Monte Carlo dosimetry-models offer improved capacity to predict response to radiopharmaceuticals compared to approaches based on mean absorbed dose to the tissue. (authors)