2种方法制备靶向超声微泡对卵巢肿瘤新生血管评价的意义  

Significance of the two methods that targeted ultrasound contrast′s preparation in tumor angiogenesis

作　　者：杨钦涵[1] 罗慧[1] 向红[1] 

机构地区：[1]新疆医科大学第一附属医院妇产超声诊断科,乌鲁木齐830054

出　　处：《新疆医科大学学报》2014年第3期296-299,302,共5页Journal of Xinjiang Medical University

基　　金：新疆医科大学第一附属医院科研奖励基金(2012YFY26)

摘　　要：目的比较使用直接连接法和生物素-亲和素桥连接法制备携血管内皮生长因子受体2(VEGFR2)单抗的靶向超声微泡(MBt)对裸鼠卵巢癌移植瘤新生血管的超声显像特点及应用价值。方法建立卵巢癌细胞株SKOV3裸鼠皮下移植瘤模型;使用直接连接法和生物素-亲和素桥连接法分别制备MBt;将18只裸鼠随机分为两组,先分别注射2种方法制备的MBt,对2种方法制备的MBt进行比较。间隔60min之后,再将18只裸鼠注射MBc,对各组内MBt与MBc进行比较。分别观察2种制备方法的MBt及各组内MBt与MBc的裸鼠卵巢癌移植瘤新生血管的造影特征,并分析时间强度曲线(TIC)相关参数;采用免疫组织化学检测肿瘤组织新生血管VEGFR2的表达。结果 2种方法均成功制备携VEGFR2单抗的MBt;生物素-亲和素桥连接法制备的MBt峰值强度较直接连接法制备的MBt峰值高(P<0.05),且持续时间更长(P<0.05);各组组内MBt峰值强度均较MBc高(P<0.05),持续时间均更长(P<0.05);免疫组织化学显示:裸鼠肿瘤组织内大量条索状棕黄色VEGFR2阳性表达。结论直接连接法和生物素-亲和素桥连接法制备的携VEGFR2单抗MBt均能实现靶向分子超声显像。但在临床诊断卵巢肿瘤超声显像及微泡稳定性方面,生物素-亲和素桥连接法效果优于直接连接法。Objective To research the use of direct connection method and biotin-avidin conjugation method prepared with vascular endothelial growth factor receptor 2 （VEGFR2）of targeted ultrasound microbubble （MBt）,compared two kinds of preparation methods ultrasonic imaging characteristics and application value of targeted ultrasound microbubble in angiogenesis in ovarian transplantation tumor of nude mice. Methods The transplant tumor model of SKOV3 in nude mice was established and MBt was prepared by direct connection method and biotin-avidin conjugation method;Mice with tumor were treated with MBt with direct connection method and biotin-avidin conjugation method and MBt control microbubbles （MBc） for ultrasound contrast examination and relative parameter analysis of time-intensity curves （TIC）;VEG-FR2 expressions in angiogenesis of tumor tissues were analyzed by immunohistochemistry.Result Two methods of preparation of MBt tcarrying with VEGFR2 was prepared successfully;biotin-avidin conjuga-tion method MBt group has higher peak intensity （P ＆lt; 0.05）and longer lasting time （P ＆lt; 0.05）;MBt group has higher peak intensity （P ＆lt;0.05）and longer lasting time （P ＆lt;0.05）;Immunohistochemistry de-tected high VEGFR2 expression in angiogenesis endothelium of tumor tissues.Conclusion This study shows that comparation of direct connection and biotin-avidin conjugation method prepared with VEGFR2 of targeted ultrasound microbubble （MBt）achieve targeted molecular ultrasound imaging.In terms of the ultrasound imaging and the microbubbles stability of clinical diagnosis of ovarian tumor,biotin-avidin con-jugation method is better than direct connection method.

关 键 词：靶向超声造影剂 生物素-亲和素桥连接法 直接连接法 肿瘤新生血管 血管内皮生长因子受体2 

分 类 号：R742.1[医药卫生—神经病学与精神病学]