中文摘要：

目的探讨以VEGFR2（kinase insert domain receptor，KDR）为靶点的靶向超声微泡对裸鼠结肠癌新生血管的成像效果。方法以生物素一亲和素桥接法将特异性结合VEGF主要受体KDR的小肽K237与脂质微泡耦联构建靶向微泡，用同样方法将对照肽与脂质微泡耦联，构建对照微泡。以KDR阴性表达的人结肠癌LS174T细胞株建立人结肠癌裸鼠移植瘤模型。12只荷瘤鼠经尾静脉随机先后注射靶向微泡、对照微泡，2种微泡注射间隔30min。注射靶向微泡后5min和注射对照微泡后5min荷瘤鼠均行超声造影检查，观察各组微泡在肿瘤组织造影增强情况，测量肿瘤组织的声强度（VI）。另取6只荷瘤鼠预先注射K237肽后再注射靶向微泡，观察微泡的成像效果。靶向微泡组、对照微泡组、小肽预先封闭组肿瘤组织的VI值比较采用单因素方差分析，组间多重比较采用最小显著性差异t检验。用免疫组织化学技术检测KDR在肿瘤组织表达及分布规律。结果成功制备了靶向微泡。注射超声微泡后5min超声检查显示靶向微泡组肿瘤组织超声造影明显增强，对照微泡组及小肽预先封闭组仅见轻度的超声造影增强。3组VI值差异有统计学意义（F=39．130，P〈0．01）。靶向微泡组与对照微泡组VI值差异有统计学意义（30．18±9．56与8．28±4．74，t=6．91，P〈0．01）；小肽预先封闭组VI值与靶向微泡组差异有统计学意义（9．23±3．44与30．18±9．56，t=4．91，P〈0．01）。免疫组织化学结果显示，荷瘤鼠结肠癌新生血管内皮细胞KDR表达较正常组织血管内皮细胞KDR表达显著增加。结论以KDR为靶点的靶向超声微泡可以与荷瘤鼠肿瘤新生血管内皮特异性黏附并有效评价肿瘤新生血管形成。

英文摘要：

Objective To evaluate the effect of tumor neovascularization imaging in a nude mouse model of colon cancer by contrast ultrasound molecular imaging （UMI） of VEGF receptor 2 （ kinase insert domain receptor, KDR）. Methods Targeted microbubbles （MBt） were built by conjugating K237, a small peptide with high affinity for KDR, to liposome microbubbles through a biotin-avidin bridge. Control microbubbles （MBc） with control peptide were prepared by the same method. Nude mice models of LS174T human colon cancer were established. MBt and MBc were injected intravenously in twelve mice in random order with an interval of 30 min. MBt were injected in another six mice after K237-peptide blocking. UMI was performed in all mice at 5 min postinjection to observe the imaging difference and measure the video intensity （VI） of tumor tissues in different groups. One-way analysis of variance and the least significant differencet test were performed to analyze the difference of tumor VI in the groups with MBt, MBc and K237 blocking. Immunohistochemistry was applied to detect the expression and distribution of KDR in tumor tissue and adjacent tumor tissues. Results K237 peptide was successfully conjugated to the surface of microbubbles through biotin-avidin mediation. Ultrasound imaging signal of the tumor was high in the MBt group, while there were no significant enhancement in the groups of K237 blocking and MBc. The VI in MBt, MBc and K237 blocking groups was significantly different （ F = 39. 130, P 〈 0.01 ）. There was a significant differ- ence of VI in the MBt group compared to the MBc group （30.18±9.56 vs 8.28 ±4.74, t =6. 91, P 〈 0. 01 ）. In the K237 blocking group VI was significantly lower than that in the MBt group （9.23 ± 3.44 vs 30.18±9.56, t =4. 91, P 〈0. 01 ）. Immunohistochemistry results showed that KDR was highy expressed in tumor tissue. Conclusions KDR-targeting liposome contrast mierobubbles may specifically and efficient- lv link to tumor vascular endothelial cells in vivo.