Comparative in vitro microdosimetric study of murine- and human-derived cancer cells exposed to alpha particles

Diffusing alpha-emitter radiation therapy (DaRT) is a proposed new form of brachytherapy using α particles to treat solid tumors. The method relies on implantable ²²⁴Ra-loaded sources that continually release short-lived α-particle-emitting atoms that spread inside the tumor over a few millimeters. This treatment was demonstrated to have a significant effect on tumor growth in murine and human-derived models, but the degree of tumor response varied across cell lines. Tumor response was found to correlate with the degree of radionuclide spread inside the tumor. In this work we examined the radiosensitivity of individual cells to determine its relationship to tumor response. Cells were irradiated in vitro by α particles using a ²²⁸Th irradiator, with the mean lethal dose, D₀, estimated from survival curves generated by standard methods. The results were further analyzed by microdosimetric tools to calculate z₀, the specific energy resulting in a survival probability of 1/e for a single cell, which is considered to better represent the intrinsic radiosensitivity of individual cells. The results of the study demonstrate that, as a rule, tumors that respond more favorably to the DaRT treatment are also characterized by higher intrinsic cellular radiosensitivities, with D₀ ranging from 0.7 Gy to 1.5 Gy for the extreme cases and z₀ following the same trend.