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

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。

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

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.