^(125)I-USPIO-bevacizumab用于肝细胞肝癌的SPECT/CT/MRI多模态显像研究

Rearch of ^(125)I-USPIO-Bevacizumab for Hepatocellular Carcinoma SPECT/CT/MRI Imaging

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.