Evidence of Extranuclear Cell Sensitivity to Alpha-particle Radiation Using a Microdosimetric Model - I - Presentation and Validation of a Microdosimetric Model

For short-range high-LET radiation therapy, the biological effects are strongly affected by the heterogeneity of the specific energy distribution delivered to tumor cells. Three-dimensional information at the cellular level is ideal for this type of study, but it is extremely difficult to obtain. In this paper, a novel microdosimetry analysis, which obtains the specific energy distribution directly from the morphological information in individual autoradiographic sections, is applied to in vivo human glioblastoma multiforme and normal brain tissue in boron neutron capture therapy. Specific energy distributions were obtained for both specimens, and they are consistent with a uniform boron microdistribution. We also used a biophysical model for cell survival analysis based on the specific energy and were able to bridge it with the model based on the corresponding macroscopic parameter (dose) using existing experimental data. The survival constant for the microscopic model was determined; cell survival curves were predicted for uniform and non-uniform source distributions, i.e., sources and cell nuclei bound together totally or only partially. The results indicate that the behavior of the survival curve can vary widely, which may have important clinical implications.JRC.E.5-Nuclear chemistr