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血管内皮生长因子C靶向分子探针在肝细胞癌大鼠模型中的特异性磁共振成像及临床意义
Specific magnetic resonance imaging of vascular endothelial growth factor-C targeted molecular probe and its clinical significance in a rat model of hepatocellular carcinoma
文章发布日期:2018年06月07日  来源:  作者:潘奇,罗春海,马婉玲,等  点击次数:325次  下载次数:41次

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【摘要】:目的 观察血管内皮生长因子C(VEGF-C)抗体与超顺磁性氧化铁颗粒(USPIO)连接的靶向分子探针(VEGF-C-USPIO)在大鼠肝细胞癌(HCC)模型体内的MR成像特点,并探讨其临床意义。方法 采用诱导法建立大鼠原位肝癌模型,将30只SD大鼠随机分为实验组(n=20)和对照组(n=10)。分别于鼠尾静脉注射靶向探针VEGF-C-USPIO和非靶向探针USPIO,并于注射前及注射后1 h对大鼠行MR扫描成像,测量其肝脏肿瘤与周围肝组织的T2WI信号强度,计算噪声比(CNR),比较增强前后2组之间CNR的差异。扫描结束后取动物肝脏进行HE染色明确大鼠肝癌病理类型;普鲁士蓝染色验证肿瘤组织细胞中铁含量;免疫组化染色验证肝癌组织中VEGF-C的表达情况。实验组与对照组间的比较采用独立样本t检验,实验组或对照组内注射对比剂前后的比较采用配对样本t检验。结果 30只大鼠全部诱癌成功,病理学诊断为HCC,成瘤率100%。实验组注射靶向对比剂VEGF-C-USPIO后1 h与注射前CNR比较,差异有统计学意义(2.11±0.23 vs 3.47±0.45,t=-13.15,P<0.001);对照组注射非靶向对比剂USPIO后1 h与注射前CNR之间差异无统计学意义(3.51±0.14 vs 3.82±0.61,t=-1.40,P=0.192);2组大鼠注射对比剂后的CNR比较,差异有统计学意义(t=17.60,P<0.001)。对大鼠肝脏标本行HE染色,结果证实为HCC;免疫组化染色显示,VEGF-C主要在肝癌细胞胞膜及胞浆中表达;普鲁士蓝染色显示,实验组肿瘤组织内蓝染铁颗粒较对照组明显增多。结论 所合成的分子靶向探针VEGF-C-USPIO对大鼠HCC模型具有较好的主动靶向作用,能够通过MR信号强度的变化实现HCC的特异性成像,为HCC的早期诊断提供影像学依据。
【Abstract】:Objective To investigate the magnetic resonance (MR) imaging features of the targeted molecular probe with vascular endothelial growth factor-C (VEGF-C) antibody and superparamagnetic iron oxide (USPIO), VEGF-C-USPIO, in a rat model of hepatocellular carcinoma (HCC) and its clinical significance. Methods The induction method was used to establish a rat model of in situ HCC, and 30 Sprague-Dawley rats were randomly divided into experimental group with 20 rats and control group with 10 rats. The rats in the experimental group were treated with tail vein injection of the targeted molecular probe VEGF-C-USPIO, and those in the control group were treated with tail vein injection of the non-targeted probe USPIO. MR scanning was performed before injection and at 1 hour after injection; the intensity of T2WI signal in liver tumor and adjacent liver tissue was measured; contrast-to-noise ratio (CNR) was calculated, and the two groups were compared in terms of CNR before and after enhancement. Liver tissue was collected after scanning, and HE staining was performed to clarify the pathological type of liver cancer in rats; Prussian blue staining was performed to analyze the content of iron in tumor cells; immunohistochemical staining was performed to investigate the expression of VEGF-C in liver cancer tissue. The independent samples t-test was used for comparison between the experimental group and the control group, and the paired samples t-test was used for comparison within each group after the injection of contrast agent. Results Cancer was successfully induced in all 30 rats; the pathological diagnosis was HCC, and the tumor formation rate was 100%. The experimental group had a significant change in CNR at 1 hour after the injection of the targeted contrast agent VEGF-C-USPIO (2.11±0.23 vs 3.47±0.45, t=-13.15, P<0.001), while the control group had no significant change in CNR at 1 hour after the injection of the non-targeted contrast agent USPIO (3.51±0.14 vs 3.82±0.61, t=-1.40, P=0.192); there was a significant difference in CNR between the two groups after injection (t=17.60, P<0.001). HE staining performed for liver tissue samples showed a pathological type of HCC; immunohistochemical staining showed that VEGF-C was mainly expressed in the membrane and cytoplasm of hepatoma cells; Prussian blue staining showed that compared with the control group, the experimental group had a significant increase in iron particles in tumor tissue. Conclusion The synthesized targeted molecular probe VEGF-C-USPIO has a good active targeting effect on a rat model of HCC and can realize the specific imaging of HCC through the change in MR signal intensity. Therefore, it provides an imaging basis for the early diagnosis of HCC.
【关键字】:癌,肝细胞;血管内皮生长因子C;磁共振成像;超小型超顺磁性氧化铁;大鼠,Sprague-Dawley
【Key words】:carcinoma, hepatocellular; vascular endothelial growth factor C; magnetic resonance imaging; ultrasmall superparamagnetic iron oxide nanoparticles; rats, Sprague-Dawley
【引证本文】:PAN Q, LUO CH, MA WL, et al. Specific magnetic resonance imaging of vascular endothelial growth factor-C targeted molecular probe and its clinical significance in a rat model of hepatocellular carcinoma[J]. J Clin Hepatol, 2018, 34(7): 1492-1496. (in Chinese)
潘奇, 罗春海, 马婉玲, 等. 血管内皮生长因子C靶向分子探针在肝细胞癌大鼠模型中的特异性磁共振成像及临床意义 [J]. 临床肝胆病杂志, 2018, 34(7): 1492-1496.

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