Enhanced IUdR radiosensitization by 241Am photons relative to 226Ra and 125I photons at 0.72 Gy/hr.

The dependence of IUdR radiosensitization on photon energy was investigated by irradiating Chinese hamster cells in vitro under aerobic conditions at a dose rate of 0.72 Gy/hr which is typical of temporary brachytherapy implants. It had been observed previously that the IUdR radiosensitization with the 60 keV photons from 241Am is about 1.5 times greater than that with 830 keV (average) photons from 226Ra. It was hypothesized that the enhanced IUdR radiosensitization for 60 keV photons was a result of a larger production of Auger electron cascades from the filling of K-shell vacancies in the iodine atoms, which have a K-shell binding energy of 33.2 keV. Since most of the photons from a 125I source have energies below 33.2 keV, it would be expected that IUdR radiosensitization with 28 keV (average) photons from 125I and 830 keV (average) photons from 226Ra would both be smaller than the radiosensitization with the 60 keV photons from 241Am. To test this hypothesis we compared IUdR radiosensitization for 226Ra, 241Am, and 125I at 0.72 Gy/hr, using Chinese hamster lung cells in vitro. The measured survival curves led to RBEs of 1.20 +/- 0.10 and 1.30 +/- 0.11 for 241Am and 125I photons relative to 226Ra; to IUdR radiosensitization factors at a 10(-5) M concentration of 1.35 +/- 0.11, 1.67 +/- 0.09, and 1.47 +/- 0.08 for 226Ra, 241Am, and 125I, respectively; and to radiosensitization factors at a 10(-4) M concentration of 1.89 +/- 0.16, 3.04 +/- 0.13, and 2.48 +/- 0.17 for 226Ra, 241Am, and 125I, respectively. These results indicate that IUdR produces significant radiosensitization with all three isotopes (226Ra, 241Am, and 125I) for continuous low dose rate irradiations at 0.72 Gy/hr. Also, we observed greater radiosensitization with 241Am photons compared to 226Ra on the higher energy side and to 125I on the lower energy side. These findings support the concept that photon-induced Auger electrons produce a significant increase in IUdR radiosensitization when photons with energies just above the K-edge of the iodine atom are employed for continuous low dose rate irradiations. These findings suggest that regimens combining IUdR infusion with temporary brachytherapy implants using low energy photons in relatively quiescent sites such as brain tumors may have clinical potential, and indicate the need for rigorous preclinical evaluation of this approach.