125I-USPIO-bevacizumab用于肝细胞肝癌的SPECT/CT/MRI多模态显像研究 |
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引用本文: | 赵焱昭,姚琦,吴冰,谭辉,邬鹏跃,张春富,程登峰,石洪成.125I-USPIO-bevacizumab用于肝细胞肝癌的SPECT/CT/MRI多模态显像研究[J].中国临床医学,2013(6):828-832. |
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作者姓名: | 赵焱昭 姚琦 吴冰 谭辉 邬鹏跃 张春富 程登峰 石洪成 |
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作者单位: | [1]复旦大学附属中山医院核医学科,上海200032 [2]上海市影像医学研究所,上海200032 [3]上海交通大学Med—X研究院,上海201101 |
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基金项目: | 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) |
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摘 要: | 目的:探讨125I标记的超小超顺磁性氧化铁颗粒(ultrasmall superparamagnetie 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2h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2h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-bevacizurnab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 T2WI加权显像.结果:”5I-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2h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 T2WI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.
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关 键 词: | 125I 超顺磁性氧化铁纳米颗粒 贝伐珠单抗 肝细胞肝癌 多模态呈像 |
Rearch of 125I-USPIO-Bevacizumab for Hepatocellular Carcinoma SPECT /CT/ MRI Imaging |
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Institution: | ZHAO Yanzhao,YAO Qi,WU Bing,TAN Hui,WU Pengyue,ZHANG Chunfu,CHENG Dengfeng( 1.Department of Nuclear Medince,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Shanghai Institute of Medical Imaging,Shanghai 200032,China; 2.Med-X Research Institute,Shanghai Jiao Tong University,Shanghai 201101,China;) |
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Abstract: | 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. |
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Keywords: | 125I Ultrasmall superparamagnetic iron oxide Bevacizumab Hepatocellular Carcinoma Muli-modalimaging |
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