Evidence of extranuclear cell sensitivity to alpha-particle radiation using a microdosimetric model. I. Presentation and validation of a microdosimetric model.

A microdosimetric model that makes it possible to consider the numerous biological and physical parameters of cellular alpha-particle irradiation by radiolabeled mAbs was developed. It allows for the calculation of single-hit and multi-hit distributions of specific energy within a cell nucleus or a whole cell in any irradiation configuration. Cells are considered either to be isolated or to be packed in a monolayer or a spheroid. The method of calculating energy deposits is analytical and is based on the continuous-slowing-down approximation. A model of cell survival, calculated from the microdosimetric spectra and the microdosimetric radiosensitivity, z(0), was also developed. The algorithm of calculations was validated by comparison with two general Monte Carlo codes: MCNPX and Geant4. Microdosimetric spectra determined by these three codes showed good agreement for numerous geometrical configurations. The analytical method was far more efficient in terms of calculation time: A gain of more than 1000 was observed when using our model compared with Monte Carlo calculations. Good agreements were also observed with previously published results.