携VEGFR2靶向超声微泡在肾癌裸鼠模型中的显像研究

Effect of contrast-enhanced ultrasound imaging of VEGFR2 targeted microbubbles in murine renal tumor model

目的评价携血管内皮生长因子受体2(VEGFR2)抗体的靶向超声微泡在原位移植裸鼠肾癌模型中的显像效果。方法建立人肾透明细胞癌原位移植裸鼠模型,制备携VEGFR2抗体的靶向微泡(MBV)及携同型抗体IgG的对照微泡(MBC),每只裸鼠分别注射MBV及MBC(顺序随机,注射时间间隔30min)后行超声造影检查,比较注射两种微泡后10min内肿瘤的增强强度,并对肿瘤组织行VEGFR2免疫组化检测。结果超声造影示注射微泡后10s时两种微泡增强强度上升百分比比较差异无统计学意义,注射微泡后1,2,4,6,8,10min时MBV增强强度上升百分比明显高于MBC(P<0.05)。免疫组化显示肾肿瘤血管内皮VEGFR2高表达。结论应用携VEGFR2抗体的靶向微泡与肾癌新生血管内皮靶点特异性结合,能持续增强显像,可作为评价肿瘤新生血管及监测抗血管治疗疗效的重要分子成像方法。

Objective To investigate the effect of contrast-enhanced ultrasound imaging of microbubbles targeted to vascular endothelial growth factor receptor type 2 （VEGFR2） in murine renal tumor model. Methods The orthotopic renal tumor model was establised in nude mice with human renal clear cell carcinoma （RCC） cell line. The microhuhbles which carried VEGFR2 antibody （MBv） and a specificity control IgG antibody （MBc） were prepared. These two different types of microbubhle were injected respectively into each mouse at random order and 30 min interval. The enhanced ultrasound images in tumors were compared after microbubble injection in 10 min. The expression of VEGFR2 in tumors was detected by immunohistochemistry. Results There was no significant difference of contrast enhancement ratios （CERs） between the two types of mierobubble at 10 s after injection, the CERs in MBv group was significantly higher than that in MBc group at 1,2,4,6,8 and 10 min after injection, respectively （P〈0.05）. The results of immunohistochemistry showed high expression of VEGFR2 in renal tumor blood vessels. Conclusion The microbubbles targeted to VEGFR2 can specially attach to the specific site in neovascular endothelium of RCC and can enhance ultrasound imaging persistently, which may provied an important method for the evaluation of tumor neovascularization and monitoring therapeutic effect of anti-angiogenesis.