VEGF-C 靶向 USPIO 在大鼠肝癌特异性 MR 成像中的价值  

Specific MR imaging of hepatocellular carcinoma with VEGF-C targeted USPIO probe in a rat model

作　　者：王琳琳[1] 于德新[1] 杨传红[1] 王青[1] 马祥兴[1] 

机构地区：[1]山东大学齐鲁医院放射科,山东济南250012

出　　处：《实用放射学杂志》2014年第8期1392-1395,共4页Journal of Practical Radiology

基　　金：中国博士后科学基金（2012M521347）;山东省自然科学基金（ZR2012HM012）.

摘　　要：目的：探讨血管内皮生长因子 C（VEGF-C）靶向超小型超顺磁性氧化铁（USPIO）分子探针在大鼠肝癌特异性 MR 成像中的价值。方法胺基修饰的 USPIO 连接 VEGF-C 抗体后构建 VEGF-C-USPIO 靶向分子探针。CCK-8法检测该探针对 HepG2肝癌细胞活性的影响。构建大鼠原位肝癌模型并随机分为 VEGF-C-USPIO 组和 USPIO 组（每组3只）,分别于尾静脉注射 VEGF-C-USPIO 或 USPIO,并于注射前、注射后0.5 h、1 h 及1.5 h 进行 MR 成像,测量肿瘤 T2 WI 及 T2＊ WI 的信号强度,并分析2组增强前后各时间点上述测量值的差异。普鲁士蓝及免疫组化染色分别对肿瘤细胞铁含量及 VEGF-C 的表达情况进行验证。结果细胞毒性实验显示,不同浓度梯度、不同孵育时间 VEGF-C-USPIO 对 HepG2细胞的细胞活力影响均较小。动物实验显示,VEGF-C-USPIO 注射后较注射前肝癌 T2 WI 及 T2＊ WI 的信号强度均明显下降,信号强度差异有统计学意义（P 〈0.05）,其中增强后1 h下降程度最低；而注射 USPIO 后肝癌信号强度下降不明显,差异无统计学意义（P 〉0.05）；靶向组与非靶向组之间肿瘤强化后的T2 WI 及 T2＊ WI 信号强度差异也具有统计学意义（P 〈0.05）。普鲁士蓝染色显示,靶向组肿瘤组织内见较多铁染色颗粒,非靶向组肿瘤组织内铁染色颗粒较少。结论 VEGF-C-USPIO 分子探针的细胞毒性小,对大鼠原位肝癌具有较好的主动靶向作用,实现了肝癌的特异性成像,同时也基于此反映肿瘤的转移能力。Objective To investigate the potential value of VEGF-C targeted ultrasmall superparamagnetic particles of iron oxide （USPIO）molecular probe in specific detection of hepatocellular carcinoma （HCC）in a rat model using MRI.Methods The targeted probe was synthesized by conjugating VEGF-C antibody with amino modified USPIO.Cell counting kit-8 assay was conducted to ascertain the probe’s effect on the growth of HepG2 cells.Rat models with HCC were divided into two groups （targeted group with VEGF-C-USPlO and a contrast with USPIO）with 3 rats for each group at random.Pre-and post-contrast enhanced MR imaging with different time points of 0.5,1 and 1.5h was performed with an injection into caudal vein.The signal intensities of the tumor on T2 WI and T2 ＊ WI were measured,and the differences of the signal intensities between pre-and post-enhancements or between both groups were analyzed.The iron particles within the tumors in two groups were confirmed by Prussian blue iron staining.The expression of VEGF-C in HCC was proved by immunohistochemistry.Results The signal intensities of HCC on T2 WI and T2 ＊ WI after VEGF-C-USPI0 injection were decreased obviously with a minimum value at 1 h ,indicating a significant difference （P 〈0.05）. However,those in USPIO group were decreased less without statistical differences （P 〉0.05）.Statistical differences in signal inten-sity on T2 ＊ WI after enhancement between both groups were also showed （P 〈0.05）.Prussian blue staining results showed more iron particles within the tumor tissues in VEGF-C-USPI0 group,whereas less ones in USPIO group.Immunohistochemical results showed that VEGF-C was over expressed in cytoplasm and membrane.Conclusion VEGF-C-USPI0 molecular probes can initiatively target to the liver cancer in rat models with expressed VEGF-C,which may help to achieve the specific MR imaging of HCC,indica-ting a potential of the metastasis.

关 键 词：靶向成像 血管内皮生长因子C 超小型超顺磁性氧化铁颗粒 肝细胞肝癌 

分 类 号：R735.7[医药卫生—肿瘤] R332[医药卫生—临床医学]