放射性碘标记表皮生长因子核素靶向治疗乳腺癌的实验研究

Experimental study of targeting therapy of breast cancer with ^(131)I-labeled epidermal growth factor

目的 观察放射性核素碘 (13 1I)偶联表皮生长因子 (EGF)对人乳腺癌裸鼠移植瘤的作用 ,探讨其靶向治疗乳腺癌的有效性和可行性。方法 氯胺 T法碘标EGF和人血清白蛋白 ;建立表达表皮生长因子受体 (EGFR)的人乳腺癌荷瘤裸鼠模型 ,36只裸鼠模型分为 6组 ,分别为阴性对照组、阳性对照组、13 1I EGF静脉组、13 1I 白蛋白组、13 1I组和13 1I EGF瘤内注射组 ,每组 6只。观察肿瘤生长增殖情况及放射性核素碘标EGF对正常组织脏器的放射毒副作用。结果 自第 1次给药后第 7天至第2 6天各时间段 ,13 1I EGF静脉和瘤内注射组肿瘤体积与阴性对照组、13 1I组及13 1I 白蛋白组肿瘤体积差异有统计学意义 (P <0 0 1) ;13 1I EGF静脉和瘤内注射组抑瘤率分别为 82 0 %和 80 7% ,与13 1I组和13 1I 白蛋白组比较 (抑瘤率分别为 7 4 9%、6 91% ) ,差异有统计学意义 (P <0 0 1) ;光学显微镜和透射电镜下见13 1I EGF静脉和瘤内注射组肿瘤细胞发生了一系列不可逆损害变化 ;未发现肝、肾和骨髓非特异性放射损伤。结论 经EGF转载的13 1I对人乳腺癌裸鼠移植瘤有明显抑制肿瘤细胞增殖生长的作用 ,无明显毒副作用。

Objective To investigate the effectiveness of 131 I epidermal growth factor (EGF) on the proliferation of a heterologous graft in nude mice bearing human breast infiltrating duct carcinoma. Methods EGF/ HAS was labeled with 131 I by chloramines T method. Human breast cancer xenografts with positive EGFR expression were established in nude mice. The nude mice were injected with normal saline, Epirubicin Hydrochloride, 131 I EGF, 131 I HAS, 131 I intravenously and 131 I EGF intratumoral administration respectively. The tumor growth inhibition rate was determined by measurement of tumor volume. Different examinations were carried out. Results There was remarkable significant difference of tumor volumes at 26th day among 131 I EGF trial groups, 131 I, 131 I HAS,and the negative control group. The tumor growth inhibition rate of 131 I EGF trial groups was 82.0%、80 7% respectively. Compared with the negative control group, the 131 I EGF trial groups remarkably suppressed the growth of tumor( P <0 05). Irreversible destruction of tissues in 131 I EGF groups was observed under light and electron microscope. There was no evidence of hepatotoxicity,renal toxicity and myelotoxicity in nude mice bearing human breast cancer given 131 I EGF over a 4 wk observation period. Conclusion 131 I EGF has obvious antitumor effects on a heterologous graft in nude mice bearing human breast infiltrating duct carcinoma, with little obvious side effects.