摘要
目的检测以新生血管渗漏区域为靶标(AngioSense○R 750EX,Ang750)和以缺氧肿瘤细胞表面的碳酸酐酶9为靶标Hypoxisense 680,Hyp680两种新试剂对活体肿瘤的荧光成像效果。方法应用Ang750和Hyp680两种荧光试剂分别对原发性肝肿瘤小鼠(H-ras12V转基因肝癌小鼠)、腋下移植瘤小鼠(S180,HepG2,H-ras12V转基因小鼠肝肿瘤组织)、以及背部皮下移植瘤小鼠(S180)进行活体成像,观察这两种试剂对活体肿瘤新生血管和缺氧微环境的指示效果。结果对于原发性肝肿瘤,Ang750试剂可在尾静脉注射后6h对肝肿瘤新生血管进行有效的指示,12h达到最佳检测效果。对于腋下移植瘤,Ang750试剂分别在尾静脉注射后10和6h对S180移植瘤及HepG2和H-ras12V转基因小鼠肝肿瘤组织的移植瘤的新生血管进行有效指示,24h达到最佳检测效果。对于背部皮下移植瘤,Ang750试剂可在尾静脉注射后10h对S180移植瘤新生血管进行有效的指示,24h达到最佳检测效果,但其荧光强度显著低于原发性肝肿瘤和腋下移植瘤。Hyp680试剂不能对本实验中活体肿瘤的缺氧微环境进行有效指示。结论以新生血管为靶标的荧光指示剂Ang750能够对体内肿瘤新生血管微环境进行有效的指示,但不能有效确认相邻近多发性肿瘤的大小和个数。以缺氧为靶标Hyp680对体内肿瘤缺氧微环境的指示作用没有普适性。
OBJECTIVE To investigate the fluorescence imaging efficiency of two new reagents, AngioSense（R）750EX （Ang750 ：targeting neovascular leakage area） and Hypoxisense680 （Hyp680 ：targeting the Carbonic Anhydrase IX of tumor cells in hypoxia area） of tumors in vivo. METHODS Ang750 and Hyp680 reagents were used to investigate in vivo fluorescence imaging efficiency to tumor mieroenvironment of angiogenesis and hypoxia in H-ras12V transgenic mice with primary liver tumors,mice with subaxillary transplanted tumors （S180,HepG2 and liver tumor tissues of H-ras12V transgenic mice） ,and mice with dorsal subcutaneous transplantation tumors （S180）. RESULTS For primary liver tumor, the angiogenesis of tumors could be effectively imaged at 6 h and excellent imaged at 12 h after injection of Ang750 in tail vein. For subaxillary transplanted tumors,the angiogenesis of tumors could be effectively imaged at 6 h for HepG2 tumor and translated hepatic tumor tissues of H-rasl2V transgenic mouse,at 10 h for $180 tumor,and all these tumors could be excellent imaged at 24 h after injection of Ang750 in tail vein. For the dorsal subcutaneous transplantation tumors, the an- giogenesis of tumors could be effectively imaged at 10 h and excellent imaged at 24 h for S180 tumors after injection of Ang750 in tail vein. However, the fluorescence intensity in dorsal subcutaneous transplantation tumors was much lower than that in primary liver tumors and subaxillary transplanted tumors. The tumor hypoxia microenvironment could not be effectively detected in vivo tumors after injection of Hyp680 in tail vein. CONCLUSIONS Ang750 targeting neovascular leakage area is an effective fluorescence agent for indicating in vivo tumor angiogenesis miroenvirornent, but it can not ef- fectively examine the size and number of adjacent multiple tumors. Hyp680 targeting the Carbonic Anhydrase IX has no u- niversality for indicating in vivo tumor hypoxia miroenviroment.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2015年第7期496-501,共6页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(30872950)
