CAJ | 학술논문

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。
목적：탐토혈관내피생장인자 C(VEGF-C)파향초소형초순자성양화철(USPIO)분자탐침재대서간암특이성 MR 성상중적개치。방법알기수식적 USPIO 련접 VEGF-C 항체후구건 VEGF-C-USPIO 파향분자탐침。CCK-8법검측해탐침대 HepG2간암세포활성적영향。구건대서원위간암모형병수궤분위 VEGF-C-USPIO 조화 USPIO 조(매조3지),분별우미정맥주사 VEGF-C-USPIO 혹 USPIO,병우주사전、주사후0.5 h、1 h 급1.5 h 진행 MR 성상,측량종류 T2 WI 급 T2* WI 적신호강도,병분석2조증강전후각시간점상술측량치적차이。보로사람급면역조화염색분별대종류세포철함량급 VEGF-C 적표체정황진행험증。결과세포독성실험현시,불동농도제도、불동부육시간 VEGF-C-USPIO 대 HepG2세포적세포활력영향균교소。동물실험현시,VEGF-C-USPIO 주사후교주사전간암 T2 WI 급 T2* WI 적신호강도균명현하강,신호강도차이유통계학의의(P <0.05),기중증강후1 h하강정도최저；이주사 USPIO 후간암신호강도하강불명현,차이무통계학의의(P >0.05)；파향조여비파향조지간종류강화후적T2 WI 급 T2* WI 신호강도차이야구유통계학의의(P <0.05)。보로사람염색현시,파향조종류조직내견교다철염색과립,비파향조종류조직내철염색과립교소。결론 VEGF-C-USPIO 분자탐침적세포독성소,대대서원위간암구유교호적주동파향작용,실현료간암적특이성성상,동시야기우차반영종류적전이능력。
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 as-certain 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 ex-pression of VEGF-C in HCC was proved by immunohistochemistry.Results The signal intensities of HCC on T2 WI and T2 * WI af-ter 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.