EQUIVALENCE OF CONTINUOUS AND PULSE SIMULATED LOW-DOSE RATE IRRADIATION IN 9L GLIOSARCOMA CELLS AT 37-DEGREES-C AND 41-DEGREES-C

The development of a brachytherapy technique that will use a scanning source to simulate continuous low dose rate irradiation holds the possibility of improving dose distributions and other clinically relevant factors as well as enhancing radiation safety. Rat 9L gliosarcoma cells growing in vitro have been used a model to determine the role of fraction size when individual pulses of irradiation are given at appropriate intervals to result in an overall dose rate that is identical to currently applied continuous low dose rate irradiation. With an overall dose rate of 0.5 Gy/hr, cell killing was identical for fractionation schemes of 0.25 Gy every 0.5 hr, 1.00 Gy every 2.0 hr, and 3.00 Gy every 6.0 hr. The cell sensitivity of these schemes was also identical to continuous irradiation at the same overall dose rate. Increasing the fraction size to 6.0 Gy with intervals of 12 hr increased the cytotoxicity. This breaking point was above the D(q) (3.9 Gy) of acutely irradiated 9L cells. These data support the hypothesis that continuous low dose rate irradiation can be simulated by fractionated high dose rate irradiation as long as the fraction size remains less than the D(q) of the acute radiation response of the cells and the overall dose rate remains constant. The role of simultaneous heating at 41-degrees-C during pulsed and continuous low dose rate irradiation was also investigated. Substantial sensitization was observed for both continuous low dose rate irradiation and pulse simulated low dose rate irradiation. The D(o) thermal enhancement ratios were 1.98 and 1.92, respectively. The above results demonstrate that modalities utilizing intermittent high dose rate irradiation can be designed such that they will be equivalent to continuous low dose rate irradiation, and that in either case simultaneous extended low temperature heating can greatly enhance the cytotoxic effects of these irradiations.