Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan, USA.
Int J Radiat Oncol Biol Phys. 2013 Aug 1;86(5):978-85. doi: 10.1016/j.ijrobp.2013.04.034.
To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model.
Orthotopic U87MG hGBM tumors were established in Nu-Foxn1(nu) mice and imaged weekly using a small-animal micropositron emission tomography (PET)/computed tomography (CT) system. Tumor volume was determined from contrast-enhanced microCT images and tumor metabolic activity (SUVmax) from the F18-FDG microPET scan. Tumors were irradiated 7 to 10 days after implantation with a total dose of 14 Gy in 7 consecutive days. The daily treatment was given as a single continuous 2-Gy dose (RT) or 10 pulses of 0.2 Gy using an interpulse interval of 3 minutes (PLRT). TMZ (10 mg/kg) was given daily by oral gavage 1 hour before RT. Tumor vascularity and normal brain damage were assessed by immunohistochemistry.
Radiation therapy with TMZ resulted in a significant 3- to 4-week tumor growth delay compared with controls, with PLRT+TMZ the most effective. PLRT+TMZ resulted in a larger decline in SUVmax than RT+TMZ. Significant differences in survival were evident. Treatment after PLRT+TMZ was associated with increased vascularization compared with RT+TMZ. Significantly fewer degenerating neurons were seen in normal brain after PLRT+TMZ compared with RT+TMZ.
PLRT+TMZ produced superior tumor growth delay and less normal brain damage when compared with RT+TMZ. The differential effect of PLRT on vascularization may confirm new treatment avenues for GBM.
在鼠模型中评估脉冲低剂量放疗（PLRT）联合替莫唑胺（TMZ）作为治疗放射性耐药多形性胶质母细胞瘤（GBM）的新方法的疗效。
在 Nu-Foxn1(nu) 小鼠中建立了 U87MG hGBM 肿瘤的原位模型，并使用小动物微正电子发射断层扫描（PET）/计算机断层扫描（CT）系统每周进行成像。通过对比增强微 CT 图像确定肿瘤体积，通过 F18-FDG 微 PET 扫描确定肿瘤代谢活性（SUVmax）。在植入后 7 至 10 天，用 7 天内连续给予 14 Gy 的总剂量进行放疗。每天的治疗方法是单次连续 2 Gy 剂量（RT）或 0.2 Gy 的 10 个脉冲，脉冲间隔为 3 分钟（PLRT）。在 RT 前 1 小时通过口服灌胃给予 TMZ（10 mg/kg）。通过免疫组织化学评估肿瘤血管生成和正常脑损伤。
与对照组相比，RT+TMZ 治疗可使肿瘤生长延迟 3 至 4 周，PLRT+TMZ 治疗效果最显著。PLRT+TMZ 导致 SUVmax 下降幅度大于 RT+TMZ。生存差异明显。与 RT+TMZ 相比，PLRT+TMZ 治疗后血管生成增加。与 RT+TMZ 相比，PLRT+TMZ 治疗后正常脑组织中变性神经元明显减少。
与 RT+TMZ 相比，PLRT+TMZ 治疗可使肿瘤生长延迟更明显，正常脑损伤更小。PLRT 对血管生成的不同影响可能证实了 GBM 的新治疗途径。
