摘要
目的:探讨125I标记的超小超顺磁性氧化铁颗粒(ultrasmall superparamagnetic iron oxide,USPIO)偶联的贝伐珠单抗(bevacizumab)用于HepG2肝细胞肝癌模型鼠多模态显像的可行性。方法:用125I标记bevacizumab,将其经尾静脉注射入HepG2肝细胞癌肝模型鼠,注射后2 h和24 h分别进行小动物活体SPECT/CT显像。然后,用直径小于20 nm的USPIO偶联bevacizumab,合成USPIO-bevacizumab;用125I标记USPIO-bevacizumab形成125I-USPIO-bevacizumab,将其经尾静脉注射入HepG2肝细胞癌模型鼠;注射后2 h和24 h分别行小动物SPECT/CT显像。显像结束后,处死模型鼠,采用免疫组化实验验证放射性标记的纳米颗粒的靶向性。为了验证USPIO-bevacizumab用于MRI显像的效果,将未用125I标记的USPIO-bevacizumab从尾静脉注射到到1只HepG2肝细胞癌模型鼠,分别于注射前后行活体MRI T2 WI加权显像。结果:125I-bevacizumab注射后,HepG2肝细胞癌模型鼠的Nano SPECT/CT显像及感兴趣区(ROI)定量分析显示,肿瘤的放射性吸收在2 h及24h分别为2.3%和2.5%,放射标志物集中在肿瘤边缘;而125I-USPIO-bevacizumab注射后,模型鼠肿瘤的放射性吸收在2 h及24 h分别为0.54%和1.04%,放射标志物在实体瘤呈均匀分布。肝细胞癌模型鼠MRI T2 WI加权MRI成像显示,注射显像剂后,肝脏及肿瘤部位信号均较注射前轻微减弱。免疫组化显示,HepG2肿瘤组织中有血管内皮生长因子(VEGF)的阳性表达及新生血管形成。结论:125I-USPIO-bevacizumab对HepG2肝细胞肝癌组织具有较好的生物靶向性,可作为新型双模态分子影像探针应用于肝细胞肝癌的SPECT/MRI显像研究。
Objective:To explore the feasibility of bevacizumab conjugated with 125I labeled ultrasmall superparamagnetic iron oxide (USPIO) for HepG2 tumor imaging.Methods:Firstly,bevacizumab was labeled with 125I and injected into the tail vein of a mouse with HepG2-induced hepatocellular carcinoma,and microSPECT/CT scannings were performed at 2 h and 24 h post injection.Then,bevacizumab was conjugated to USPIO with diameters less than 20 nm and then labeled with 125I.The 125I-USPIO-bevacizumab was injected into the tail vein of a mouse with HepG2-induced hepatocellular carcinoma,and microSPECT/CT scannings were performed at 2 h and 24 h after injection.After imaging,the mouse was sacrificed and the tumor was removed for immunohistological study to verify the targeting capability of 125I-USPIO-bevacizumab.Additionally,in order to test the potential of USPIO-bevacizumab as a MRI imaging probe,another one HepG2 tumored mouse was performed MRI T2WI imaging before and after injection of this probe.Results:SPECT/CT imaging of HepG2 tumored mice showed that the radioactivity of 125I-bevacizumab accumulated at the edge of the tumor; ROI analysis of tumor showed 2.3% at 2 h and 2.5% at 24 h,respectively.However,125I-USPIO-bevacizumab accumulated evenly in the tumor area with ROI of 0.54% at 2 h and 1.04% at 24 h.T2 weighted imaging by 3T Trio MRI revealed slightly darker signal in the tumor area after USPIO-bevacizumab was given to HepG2 tumored mouse than before.Expression of vascular endothelial growth factor of (VEGF) was detected in the HepG2 tumor and new vessels were also found by immunohistology.Conclusions:The 125I-USPIO-bevacizumab have good targeting capacity to HepG2 hepatocellular carcinoma,and it may be a potential novel hybrid SPECT/MRI probe for hepatocellular carcinoma imaging.
出处
《中国临床医学》
2013年第6期828-832,共5页
Chinese Journal of Clinical Medicine
基金
国家自然科学基金青年基金项目(编号:81201130)
上海市影像医学研究所基金项目(编号:Y-2013-11)