^(125)I籽粒间质内放射治疗恶性胶质瘤有效性

^(125)I seeds brachytherapy in teatment of malignant glioma:a small dose is enough

目的:探索125I籽粒间质内放射治疗恶性胶质瘤的合适剂量。方法:将C6胶质瘤株移植到雌性BALB/c无胸腺小鼠右肩皮下建立24只荷瘤鼠模型,并随机分为4组:对照组、空白籽粒组0、.4 mCi(14.8 MBq)籽粒组0、.8 mCi(29.6 MBq)籽粒组。将相应剂量的125I籽粒入肿瘤中心后,观察肿瘤生长情况并绘制肿瘤生长曲线;处死动物后,取肿瘤标本,病理组织切片H-E染色,采用流式细胞术检测细胞凋亡情况,采用免疫组织化学法测定P53蛋白表达。结果:(1)0.4 mCi籽粒组肿瘤体积较对照组及空白籽粒组小(P<0.05);0.8 mCi籽粒组较对照组、空白籽粒组及0.4 mCi籽粒组小(P<0.05);对照组与空白籽粒组无差异(P>0.05);但0.8 mCi籽粒组在种植125I籽粒后3 d内体积较其他3组大(P<0.05)。(2)125I籽粒内照射剂量达到5.8 Gy时开始出现放射性坏死,坏死面积/总面积为(18.33±16.42)%;12 Gy时为(66.67±14.97)%;24 Gy时为(75.83±10.83)%。(3)肿瘤在接受125I24 Gy剂量内照射后凋亡最多;对放射治疗最为敏感的G2-M期细胞在5.8 Gy内照射剂量下最多。(4)肿瘤细胞P53表达在对照组不明显,在3.3 Gy籽粒组和5.8 Gy籽粒组最高。结论:用立体定向技术将小剂量125I籽粒植入脑深部恶性胶质瘤有临床可行性。

Objective：To determine the proper dosage of ^125Ⅰ seed for brachytherapy of malignant glioma. Methods： C6 malignant glioma cell line was implanted subcontaneously in 24 female BALB/c nude mice and mice were allowed to grow till the diameter of the tumor reached 11 mm （7 ml）, and then the mice were randomly divided into 4 groups：control group （without therapy）, blank seed group,0.4 mCi（14.8 MBq） ^125Ⅰ seed group and 0.8 mCi（29.6 MBq） ^125Ⅰ seed group （seeds in the latter 3 groups were implanted into the center of the tumor）. The growth of the tumor was observed and the growth curve was drawn. Mice were then killed and tumor specimen was obtained for H-E staining. Cell apoptosis was observed with flow cytometry and the expression of p53 protein was dectected with immunohistochemical method. Results： The tumor volume of 0.4mCi group was smaller than those of control group and blank seed group （P〈0.05） and there was no significant difference between the latter 2 groups. The tumor volume in 0.8 mCi group was smaller than that of 0.4 mCi group（P〈0.05）. But during the first 3 d after the ^125Ⅰ seeds implantation,tumor volume of 0. 8mCi group was larger than those of the other 3 groups（P〈0. 05）. H-E staining showed that radiation necrosis began to appear at 5.8 Gy, with the percentage of necrosis area being （18.33±16.42）% at 5.8 Gy,（66.67±14.97）% at 12 Gy and （75.83±10.83）% at 24 Gy. The most severe apoptosis （[16.8±4.3]%） occurred at 24 Gy; and for G2-M stage cells, the most sensitive cells to radiotherapy, the most severe apoptois （[72. 6±5.26]%） occurred at 5.8 Gy. The expression of P53 protein was not obvious in control group and reached peak at 3.3 Gy （[71. 67±8.65]%） and 5.8 Gy （[84.75±8.87]）% in ^125Ⅰ seed group. Conclusion： It is clinically feasible to stereotaxically implant small dose of ^125Ⅰ seeds for treatment of deep brain malignant glioma.