靶向整合素α_vβ_3羟基乙酸共聚物造影剂对肿瘤血管的超声分子显像

Ultrasound molecular imaging of tumor angiogenesis with polylactic acid glycolic acid targeted to integrin α_vβ_3

目的评价靶向整合素αvβ3羟基乙酸共聚物(PLGA)造影剂对裸鼠肿瘤新生血管的超声分子显像能力。方法采用共价连接-碳二亚胺法制备出靶向整合素αvβ3的RGD-PLGA高分子造影剂,并用激光共聚焦鉴定其连接情况。建立裸鼠卵巢癌SKOV-3模型,分别经尾静脉注射靶向整合素αvβ3的RGD-PLGA造影剂(RGD-PLGA组)和PLGA普通造影剂(PLGA组)进行造影检查。记录造影情况,绘制时间-强度曲线,并对两组造影剂的持续时间和峰值强度进行统计学分析;然后对造影40min后的图像进行数字减影和彩色编码,直观观察两种造影剂的强度差异。结果成功制备出靶向整合素αvβ3的RGD-PLGA高分子造影剂。RGD-PLGA组较PLGA组持续显影时间延长,峰值强度提高。对造影40min后的图像进行数字减影和彩色编码,可直观观察到RGD-PLGA组较PLGA组增强更明显。结论靶向整合素αvβ3RGD-PLGA造影剂较普通PLGA造影剂有较好的造影效果。

Objective To evaluate CEUS with polylactic acid glycolic acid （PLGA） targeted to integrin αvβ3 for imaging tumor angiogenesis in nude mice. Methods Targeted high molecular polymer agents RGD-PLGA was synthesized by com- bining PLGA-COOH ultrasound contrast agents with RGD peptides using covalent binding, and the conjugation of FITC- RGD and PLGA was detected by laser scanning confocal microscope. SKOV-3 tumor models in nude mice were established and then underwent CEUS with RGD-PLGA （RGD-PLGA group） and control PLGA agents （PLGA group）. Sonograms were analyzed by DFY quantometer, while time-intensity curve （TIC） and statistical table were depicted according to the results of analyzing. The sonograms after injecting agents 40 min were digitally subtracted and color coded, which were used to directly observe the difference between the two kinds of sonograms. Results RGD-PLGA was successfully synthe- sized. TIC and statistical analysis showed that peak echogenicity was higher, and the time to wash out was longer in RGD- PLGA group compared with those in PLGA group. The sonograms after injecting agents 40 min directly showed that the RGD-PLGA group enhanced more apparently than PLGA group. Conclusion RGD-PLGA targeted agents are better than PLGA contrast agents for evaluating tumor angiogenesis.