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

Purpose: To investigate the impact of a time-variable dose rate during a hi gh 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 cas e of Ir-192-wires). Moreover, the kinetics of repair in rat spinal cord are 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 Ir-192-point sour ce, varying the activity of the point source bet ween 0.3 and 6.5 Ci. Three different groups of experiments are defined. var ying 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 Gp/h and 13-15 Gy/h, respecti vely. Difference in temporal dose distribution (dose rate variation) during almost the same overall treatment time is obtained by varying the number o f pulses per dwell position in either one or ten runs through the implant. For reasons of comparison, previously reported results of continuous irradi ation at a constant dose rate obtained with two Ir-192-wires in a fixed pos ition are reanalyzed. Paralysis of the hindlegs after 5-6 months and histop athological examination of the spinal cold of each animal are used as exper imental endpoints. Results: During one run of the Ir-192-point source, the peak dose rate is a t least 25 times higher as compared with the minimum local dose rate and al most four times higher as compared with the average dose rate. For the thre e different groups of varying overall treatment times and average dose rate s there is a significant difference in biological effect, with an ED50-valu e of 23.1-23.6 Gy (average dose rate 312-489 Gy/h), 25.4-27.9 Gy (average d ose rate 312-489 Gp/h) and 29.3-33 Gy (average dose rate 13-15 Gy/h). For t hese range of single doses, difference in temporal dose distribution with e ither 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 differ ence between one or ten run is no longer significant. However, the results with the Ir-192-point sourer: at an average dose rate/run of 13-15 Gy/h are significantly different from the ED50-value of 33 Gy using Ir-192-wires at the same but constant dose rate. Using different types of analysis to esti mate the repair parameters, the best fit of the data is obtained assuming b iphasic It pair kinetics and a variable dose rate (geometrically dependent) for the Ir-192-point source. On the basis of the incomplete repair LQ mode l. two repair processes with an alpha/beta ratio = 2.47 Gy and repair halft imes of 0.19 and 2.16 h are detected. The partition coefficient for the lon ger 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 frac tions with complete repair in between. Conclusions: Even in the range of high dose rates of 15-500 Gy/h, spinal co rd radiation tolerance is significantly increased by a reduction in dose ra te. For larger doses per fraction in PDR-brachytherapy dose rate variation is important, especially for tissues with very short repair half times (com ponents). In rat spinal cord the repair of sublethal damage (SLD) is govern ed by a biphasic repair process with repair halftimes of 0.19 and 2.16 h. ( C) 2000 Elsevier Science Ireland Ltd. All rights reserved.