Dependence of cell survival on iododeoxyuridine concentration in 35-keV photon-activated Auger electron radiotherapy.

Abstract

To measure and compare Chinese hamster ovary cell survival curves using monochromatic 35-keV photons and 4-MV x-rays as a function of concentration of the radiosensitizer iododeoxyuridine (IUdR). IUdR was incorporated into Chinese hamster ovary cell DNA at 16.6 ± 1.9%, 12.0 ± 1.4%, and 9.2 ± 1.3% thymidine replacement. Cells were irradiated from 1 to 8 Gy with 35-keV synchrotron-generated photons and conventional radiotherapy 4-MV x-rays. The effects of the radiation were measured via clonogenic survival assays. Surviving fraction was plotted vs. dose and fit to a linear quadratic model. Sensitization enhancement ratios (SER(10)) were calculated as the ratio of doses required to achieve 10% surviving fraction for cells without and with DNA-incorporated IUdR. At 4 MV, SER(10) values were 2.6 ± 0.1, 2.2 ± 0.1, and 1.5 ± 0.1 for 16.6%, 12.0%, and 9.2% thymidine replacement, respectively. At 35 keV, SER(10) values were 4.1 ± 0.2, 3.0 ± 0.1, and 2.0 ± 0.1, respectively, which yielded SER(10) ratios (35 keV:4 MV) of 1.6 ± 0.1, 1.4 ± 0.1, and 1.3 ± 0.1, respectively. SER(10) increases monotonically with percent thymidine replacement by IUdR for both modalities. As compared to 4-MV x-rays, 35-keV photons produce enhanced SER(10) values whose ratios are linear with percent thymidine replacement and assumed to be due to Auger electrons contributing to enhanced dose to DNA. Although this Auger effectiveness factor is less than the radiosensitization factor of IUdR, both could be important for the clinical efficacy of IUdR radiotherapy.