Comparative In Vitro Microdosimetric Study of Murine- and Human-Derived Cancer Cells Exposed to Alpha Particles

作者:Lazarov E; Arazi L*; Efrati M; Cooks T; Schmidt M; Keisari Y; Kelson I
来源:Radiation Research, 2012, 177(3): 280-287.
DOI:10.1667/RR2664.1

摘要

Lazarov, E., Arazi, L., Efrati, M., Cooks, T., Schmidt, M., Keisari, Y. and Kelson, I. Comparative In Vitro Microdosimetric Study of Murine- and Human-Derived Cancer Cells Exposed to Alpha Particles. Radiat. Res. 177, 280-287 (2012).
Diffusing alpha-emitter radiation therapy (DaRT) is a proposed new form of brachytherapy using alpha particles to treat solid tumors. The method relies on implantable Ra-224-loaded sources that continually release short-lived alpha-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 alpha particles using a Th-228 irradiator, with the mean lethal dose, D-0, estimated from survival curves generated by standard methods. The results were further analyzed by microdosimetric tools to calculate z(0), the specific energy resulting in a survival probability of lie 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 D-0 ranging from 0.7 Gy to 1.5 Gy for the extreme cases and z(0) following the same trend.

  • 出版日期2012-3