结肠癌皮下移植瘤靶向血管内皮生长因子受体2脂质微泡超声造影特征：与裸脂质微泡比较

Characteristics of VEGFR2-targeted lipid microbubbles contrast-enhanced ultrasound in nude mice with subcutaneous colonic carcinoma xenografts： compared with lipid microbubbles

目的探讨结肠癌皮下移植瘤靶向血管内皮生长因子受体2（VEGFR2）脂质微泡与裸脂质微泡超声造影特征及定量分析结果间差异。方法对30只VEFGR2高表达的结肠癌皮下种植瘤Balb／C裸鼠随机应用靶向VEGFR2脂质微泡及裸脂质微泡两种超声造影剂分别进行超声造影检查，观察两种超声造影剂的成像特征，应用定量分析软件进行超声造影定量分析，比较两种造影剂定量结果的差异。结果肉眼观察两种超声造影剂动脉期均表现为从周边到中间的向心性灌注，增强效果无明显差异；静脉期裸脂质微泡造影表现为整体低增强，而靶向VEGFR2脂质微泡消退延迟，肿瘤内仍可见结节状不均匀高增强。超声造影定量参数峰值强度、到达时间、达峰时间、平均血容量、平均血流量等指标两组间差异无统计学意义（P〉0．05），而靶向VEGFR2脂质微泡开始消退时间、完全廓清时间与裸脂质微泡比较均有延迟，差异有统计学意义（P〈0．05和P〈0．01）；靶向VEGFR2脂质微泡曲线下面积高于裸脂质微泡（P〈0．01）。结论靶向VEGFR2脂质微泡与肿瘤内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 explore the difference of the contrast-enhanced ultrasound （CEUS） and quantitative parameters between lipid mierobubbles and VEGFR2-targeted lipid mierobubbles in nude mice model with subcutaneous orthotopic transplantation colon cancer.Methods 30 Balb/C nude mice with high VEGFR2 expressed subcutaneous colonic carcinoma xenografts were enrolled in this study. CEUS was performed in each mouse with targeted and non targeted lipid microbubbles respectively.Qontrast software was used to analyze the dynamic image quantitatively.The difference of the CEUS image and quantitative parameters between the two kinds of microbuhbles was analyzed.Results Two kinds of microbubbles were characterized by perfusion from peripheral to the middle of the centripetal in the arterial phase by routine visual examination, there were no significant difference of the effect of enhancement.In the venous phase the lipid microbubble were presented as hypo-enhaneement, but the VEGFR2-targeted lipid microbubbles were presented as inhomogeneous hyper-enhancement.There were no significant difference of the parameters of peak intensity, arrive time, time to peak, regional blood volume and regional blood flow （P 〉0.05）. However,compared with the lipid microbubbles, the regression time and the clearance time of the VEGFR2- targeted lipid microbubbles had significant delay（ P 〈0.05, P 〈0.01）. The area under the curve in the VEGFR2-targeted lipid microbubbles had significant higher than lipid microbubbles（ P 〈0.01）.Conclusions The VEGFR2-targeted lipid microbubbles can specially attach to the specific site in neovascular endothelium of tumor and can enhance ultrasound imaging persistently, which may provide an important method for the evaluation of tumor neovascularization and monitoring therapeutic effect of anti-angiogenesis.