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

Abstract

Objective To explore the difference of the contrast-enhanced ultrasound (CEUS) and quantitative parameters between lipid mierobubbles and VEGFR2-targeted lipid microbubbles 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 microbubbles 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-enhancement,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. Key words: Ultrasonography ; Microbubbles ; Liposomes ; Targeted microbubbles