近红外荧光分子探针在胃癌分子成像中的应用研究

摘要

目的 评估3种近红外荧光分子探针在胃癌分子成像中的靶向性和荧光效应,为胃癌荧光分子成像筛选可用的靶向分子探针.方法 选用3种近红外荧光分子探针(IntergriSenseTM750、FolateRsenseTM680、MMPSenseTM750FAST),并以吲哚菁绿作为对照组,经裸鼠胃癌皮下移植瘤模型尾静脉注射探针后进行活体荧光分子成像,量化分析肿瘤部位荧光信号强度.离体荧光分子成像观察探针的生物分布和代谢.成像结束后,对移植瘤进行组织学及3种探针相应分子靶点(αvβ3、FRα、MMP)免疫组织化学检测.结果 活体荧光分子成像结果显示探针(IntergriSenseTM750、FolateRsenseTM680、MMPSenseTM750FAST)均在荷瘤鼠肿瘤部位出现浓聚,浓聚高峰分别在注射后1 h、1 h、24 h.与对照组相比,上述3种分子探针有较好的靶向性和信噪比.离体荧光分子成像证实探针主要经肝、肾代谢.免疫组化表明3种探针对应的分子靶点在裸鼠胃癌皮下移植瘤均有表达.结论 以上3种探针可用于胃癌荧光分子成像.αvβ3、FRα、MMP可作为胃癌荧光分子成像的靶点.%Objective To evaluate the targeting ability and fluorescence efficiency of three kinds of near infrared fluorescent probes in molecular imaging of gastric cancer,and to screen useful molecular probes for fluorescence molecular imaging of gastric cancer.Methods Three kinds of near infrared fluorescent molecular probes(IntergriSenseTM750,FolateRsenseTM680,MMPSenseTM750FAST)were used to detect and quantify the fluorescent signal intensity of tumor tissue by in vivo fluorescent molecular imaging after injecting of the above probes to subcutaneous xenograft models of gastric cancer.The biodistribution and metabolism of these probes were performed by exvivo fluorescence molecular imaging.After fluorescence molecular imaging,the histologic examination of the transplanted tumor tissue and the immunohistochemical detection of the corresponding molecular targets(αvβ3,FRα,MMP)were performed.Results In vivo fluorescence molecular imaging showed that three kinds of probes(IntergriSenseTM750,FolateRsenseTM680,MMPSenseTM750FAST)were concentrated in the tumor-bearing tumor,and the peak was 1 hour,1 hour and 24 hours after injection,respectively.Furthermore,compared with control group,the region of interest of the three targeted fluorescect probes were better.In vitro fluorescence molecular imaging confirmed that the probes was mainly metabolized by the liver and kidney.Immunohistochemistry confirmed that three molecular targets were expressed in subcutaneous xenografts models.Conclusion The above mentioned molecular probes can be used for the fluorescence molecular imaging of gastric cancer.αvβ3,FRα and MMP can be used as targets for imaging of gastric cancer.