Fu K K, Hurst S, Begg A C, Brown J M
Cancer Clin Trials. 1980 Fall;3(3):257-65.
Hypoxic cell sensitizers have been shown to enhance the radiation effects on tumors for single and multifractionated doses of radiation given in acute exposures. Low dose rate brachytherapy provides an opportunity for short-term high dose drug administration and continuous drug exposure throughout the entire brachytherapy course. To determine the effects of misonidazole during continuous low dose rate irradiation we have exposed the EMT6/SF tumor to continuous irradiation at 4.2 and 1.64 rads/minute with and without misondiazole (at doses of 1 mg/g or 0.2 mg/g), in bilaterally nephrectomized mice, and compared the results to those obtained wih acute exposures. Radiosensitization by misonidazole at a clinically achievable plasma concentration was observed during continuous low dose rate irradiation. The DMF (dose-modifying factor) varied with drug dose and dose rate. At a dose of 1 mg/g the DMF was 2.4 at 221 rads/minute and 1.6 at 4.2 rads/minute; at 0.2 mg/g it was 1.5 at 221 rads/minute and 4.2 rads/minute and 1.4 at 1.64 rads/minute. Cytotoxicity was also observed with drug exposure greater than 6 hours. Our results suggest that it would be advantageous to sue misonidazole during low dose rate brachytherapy.
低氧细胞增敏剂已被证明可增强急性暴露下单次和多次分割剂量辐射对肿瘤的效应。低剂量率近距离放射治疗为短期高剂量给药以及在整个近距离放射治疗过程中持续给药提供了机会。为了确定甲硝唑在持续低剂量率照射期间的作用，我们在双侧肾切除的小鼠中，将EMT6/SF肿瘤暴露于4.2和1.64拉德/分钟的持续照射下，同时给予和不给予甲硝唑（剂量为1毫克/克或0.2毫克/克），并将结果与急性暴露所获得的结果进行比较。在持续低剂量率照射期间观察到了临床可达到的血浆浓度下甲硝唑的放射增敏作用。剂量修正因子（DMF）随药物剂量和剂量率而变化。在1毫克/克的剂量下，221拉德/分钟时的DMF为2.4，4.2拉德/分钟时为1.6；在0.2毫克/克时，221拉德/分钟和4.2拉德/分钟时为1.5，1.64拉德/分钟时为1.4。药物暴露超过6小时也观察到了细胞毒性。我们的结果表明，在低剂量率近距离放射治疗期间使用甲硝唑将是有利的。
