以血管生成为靶点的肿瘤核素显像及治疗的实验研究

Nuclide imaging and treatment targeting at angiogenesis of tumors

目的 以荷人膀胱癌、胆管癌小鼠为模型 ,研究血管内皮生长因子 (VEGF)及其受体KDR、整合素αvβ3 受体在肿瘤的核素显像及治疗中的应用。方法 ①复制荷人膀胱癌小鼠模型 ,观察 13 1I anti VEGF的放射免疫显像 ;②将荷瘤小鼠分为实验组、非标记抗体对照组及空白对照组 ,探讨 13 1I anti KDR的放射免疫治疗 ;③建立荷人胆管癌小鼠模型 ,观察12 5I RGD 4CY的受体显像。结果 ①免疫组化结果示膀胱癌组织高表达VEGF及KDR蛋白 ,而正常组织极低水平表达 ;②13 1I anti VEGF、13 1I anti KDR及 12 5I RGD 4CY在各组织中均具有较高的T/NT ;③ 13 1I anti KDR的放射免疫治疗示实验组与非标记抗体对照组均能明显抑制膀胱癌的生长 ,但前者作用快且抑制率明显高于后者 ;④放射自显影示 12 5I RGD 4CY在肿瘤组织中浓聚影最强 ,肺、颈部及其它软组织呈低水平分布。结论 13 1I anti VEGF、13 1I anti KDR可较好地显示膀胱癌 ,并明显抑制其生长 ,12 5I RGD 4CY可望成为一有效的肿瘤αvβ3 受体显像剂。

Objective To investigate the application of vascular endothelial growth factor (VEGF) and its receptor KDR and α vβ 3 receptor in nuclide imaging and treatment of nude mice bearing human bladder cancer and cholangiocarcinoma. Methods ① Model of nude mice bearing bladder cancer was duplicated. Radioimmunoimaging (RII) of 131I-anti-VEGF was observed. ② Nude mice bearing bladder cancer were randomly divided into experimental group, anti-KDR monoclonal antibodies group, and saline control group. The radioimmunotherapy (RIT) of 131I-anti-KDR was explored. ③ Model of nude mice bearing cholangiocarcinoma was established and α vβ 3 receptor scintigraphy was studied. Results ① The study of immunohistochemistry showed that VEGF and its receptor KDR were highly expressed in bladder cancer, but their expressions were very low in normal tissues. ② T/NT of 131I-anti-VEGF, 131I-anti-KDR and 125I-RGD-4CY in all tissues was high. ③ RIT of 131I-anti-KDR showed that the growth of bladder was significantly suppressed in the experimental group and anti-KDR monoclonal antibody group, but the suppression ratio in the experimental groups was superior to that in the anti-KDR monoclonal antibody group. ④ Autoradiography showed that the 125I-RGD-4CY activity was the highest in tumor, and there was low level of radioactive distribution in the lungs, neck, and other soft tissues. Conclusion Bladder cancer can be perfectly imaged with 131I- anti-VEGF, 131I- anti-KDR. 125I-RGD-4CY is a potential tracer for tumor α vβ 3 receptor scintigraphy.