^(125)Ⅰ籽源薄层片植入治疗小鼠移植瘤的效果及可行性研究

Effect and Feasibility in Treating Tmnor-bearing Mice with ^(125) I Seeds Carrier Sheet

目的：采用^(125) Ⅰ籽源薄层片在荷瘤鼠体内模拟临床植入治疗肿瘤残基，观察对肿瘤的抑制效果、可行性和安全性。方法：小鼠皮 下接种艾氏腹水瘤细胞后24 h，治疗组在接种部位分别植入1粒表观活度为23． 3 MBq(O．63 mCi)和29． 6 MBq(0． 8 mCi)二种剂量 的^(125) Ⅰ籽源薄层片，对照组植入无放射活性的空籽源薄层片。治疗15 d，测量肿瘤体积并绘制肿瘤生长曲线。处死小鼠后称取瘤重并 计算肿瘤抑制率。流式细胞仪检测和电镜观察肿瘤细胞的凋亡情况，常规病理切片观察对肿瘤组织的破坏程度、载体支架周围的组 织反应等。结果：治疗15 d，动态观察^(125) Ⅰ籽源薄层片的抑瘤效果显示，2个治疗组随治疗时间的延长，照射累积剂量增加，抑瘤效果 显著增加，成瘤率分别是63． 6%和63． 6%(对照组100%)，肿瘤倍增时间从1． 6 d 延长为2． 74 d 和2． 84 d，抑瘤率分别为63． 0%和75． 8%，凋亡率较对照组显著增加约2倍(P＜0． 001) 。电镜超微结构观察显示肿瘤细胞出现核固缩、染色质边集和凋亡小体，但2个治 疗组间无显著差异。病理切片显示，^(125) Ⅰ籽源薄层片周围从内向外有少量炎症细胞浸润，纤维组织增生包裹了载体支架阻止了籽源的 移位；邻近籽源的肿瘤细胞由凝固性坏死向外逐渐减弱为变性坏死；其它周围组织无明显变化。结论：^(125) Ⅰ籽源薄层片能明显抑制小 鼠艾氏腹水瘤生长，促进肿瘤细胞凋亡，是植入治疗肿瘤残基切实可行又安全的方法。

Objective： To investigate the inhibitory effect, feasibility and safety in treating tumor-beating mice with 125^I seeds carrier sheet, as a simulation of clinical tumor bed brachytherapy. Methods： 24h after subcutaneous injection of Ehrlich ascites cancer （EAC） cells, mice were divided into one control group and two treatment groups. For treatment group 1 and 2,each mouse was implanted with 125^I seeds carrier sheet with apparent activity of 23. 3MBq and 29. 6MBq respectively. While for control group, each mouse was implanted with dummy seeds carrier sheet instead. All 125^I seeds carrier sheet were located at the same place where EAC cells were injected. The tumor volumes were measured to obtain tumor growth curve. After a treatment span of 15 days, all mice were sacrificed and tumor weights were measured to obtain tumor suppression rate. Flow cytometry and transmission electron microscopy were used to observe apoptosis in tumor cells. Pathological changes of tumor tissue were observed under light microscope to evaluate the destruction of tumor tissue and peripheral tissue reactivity. Results： In the 15-day treatment, tumor suppression rate in the two treatment groups were 75.8% and 63.0% respectively（P〉 0. 05）, Tumor volume doubling time in treatment group prolonged from 1.6d to 2.8d（P〈0. 001）. Apoptosis rate was significant higher in treatment group than that in control group（P〈0. 001）. Cellular nucleus shrinking, nucleus fragments, uniform chromatin agglutinating and apoptotic body were seen under transmission electron microscopy. No significant difference was observed between the two treatment groups. Routine pathology showed slight infiltration of inflammatory cells and hyperplasia of fibrous tissue near 125^I seeds carrier sheet. Accompanied by the increase of distance, tumor cells adjacent to seeds vary from coagulative necrosis to degenerative necrosis. No significant change was observed in other tissues. Conclusion： 125^I seeds carrier sheet brachytherapy significantly inhibits the growth of ghrlich ascites cancer cells and promotes apoptosis of tumor cells. It should be a feasible and safe brachytherapy method in treating clinical unresectable residual tumor.