Radiation tolerance of rat spinal cord to pulsed dose rate (PDR-) brachytherapy: the impact of differences in temporal dose distribution

Abstract

Purpose: To investigate the impact of a time-variable dose rate during a high dose rate (HDR-) or pulsed dose rate (PDR-) brachytherapy fraction with the HDR-microSelectron and to compare this with the biological effect of a constant dose rate treatment with the same average dose rate (as in the case of 192Ir-wires). Moreover, the kinetics of repair in rat spinal cord are investigated using a wide spectrum of temporal dose distributions. Materials and methods: Two parallel catheters are inserted on each side of the vertebral bodies of the rat spinal column (Th 10–L 4) and connected to the HDR-microSelectron. Interstitial irradiation (IRT) is performed with a stepping 192Ir-point source, varying the activity of the point source between 0.3 and 6.5 Ci. Three different groups of experiments are defined, varying the overall treatment time and average dose rates in the range of 3–8, 28–53 and 82–182 min and 312–489 Gy/h, 32–56 Gy/h and 13–15 Gy/h, respectively. Difference in temporal dose distribution (dose rate variation) during almost the same overall treatment time is obtained by varying the number of pulses per dwell position in either one or ten runs through the implant. For reasons of comparison, previously reported results of continuous irradiation at a constant dose rate obtained with two 192Ir-wires in a fixed position are reanalyzed. Paralysis of the hindlegs after 5–6 months and histopathological examination of the spinal cord of each animal are used as experimental endpoints. Results: During one run of the 192Ir-point source, the peak dose rate is at least 25 times higher as compared with the minimum local dose rate and almost four times higher as compared with the average dose rate. For the three different groups of varying overall treatment times and average dose rates there is a significant difference in biological effect, with an ED 50-value of 23.1–23.6 Gy (average dose rate 312–489 Gy/h), 25.4–27.9 Gy (average dose rate 312–489 Gy/h) and 29.3–33 Gy (average dose rate 13–15 Gy/h). For these range of single doses, difference in temporal dose distribution with either one or ten runs is only significant for treatment times less then 1 h. For the prolonged treatment times at lower average dose rates, the difference between one or ten run is no longer significant. However, the results with the 192Ir-point source at an average dose rate/run of 13–15 Gy/h are significantly different from the ED 50-value of 33 Gy using 192Ir-wires at the same but constant dose rate. Using different types of analysis to estimate the repair parameters, the best fit of the data is obtained assuming biphasic repair kinetics and a variable dose rate (geometrically dependent) for the 192Ir-point source. On the basis of the incomplete repair LQ model, two repair processes with an α/β ratio=2.47 Gy and repair halftimes of 0.19 and 2.16 h are detected. The partition coefficient for the longer repair process is 0.98. This results in the proportion of total damage associated with the longer repair halftime being 0.495 for short sharp fractions with complete repair in between. Conclusions: Even in the range of high dose rates of 15–500 Gy/h, spinal cord radiation tolerance is significantly increased by a reduction in dose rate. For larger doses per fraction in PDR-brachytherapy dose rate variation is important, especially for tissues with very short repair half times (components). In rat spinal cord the repair of sublethal damage (SLD) is governed by a biphasic repair process with repair halftimes of 0.19 and 2.16 h.