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顺磁性抗HER2免疫脂质体的制备及MR靶向成像研究

Preparation of paramagnetic anti-HER2 immunoliposome and MR targeted imaging
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摘要 目的:制备顺磁性抗HER2免疫脂质体,探讨其对荷人乳腺癌裸鼠模型的MR特异成像作用。方法:制备顺磁性抗HER2免疫脂质体,评价其理化特性及体外细胞结合特性。动物试验选择12只荷人乳腺癌裸鼠,分为2组进行磁共振扫描。实验组为顺磁性抗HER2免疫脂质体组,对照组为钆布醇组。测量平扫及静脉注射对比剂后第10分钟、1小时、6小时后,肿瘤组织在T1WI的信号强度,计算并比较不同实验组内肿瘤组织的强化率和对比度噪声比。结果:顺磁性抗HER2免疫脂质体的平均粒径为134.2nm,多分散系数为0.29,Zeta电位为-32.49mV,r1弛豫率为4.67/mM·s;与HER2高表达的SK-BR-3乳腺癌细胞表现为特异性结合,胞浆出现罗丹明红染。注射顺磁性抗HER2免疫脂质体后,肿瘤组织表现为显著持久的强化;增强10min后肿瘤强化率为121%,1h后肿瘤强化率为185%,6h后肿瘤强化率为224%。对照组在静脉注射钆布醇10min后,肿瘤组织表现为显著强化,强化率为153%,1h后的信号强度与平扫相近。两组实验动物在注射对比剂后第1、6h后,肿瘤组织的强化率、CNR差异具有统计学意义。结论:顺磁性抗HER2免疫脂质体具有长循环时间,高r1弛豫率,对乳腺癌具有特异性靶向作用。 Objective:To prepare paramagnetic anti-HER2 immunoliposome,and to study its specific character in MR imaging using nude mice bearing human breast cancer model.Methods:Paramagnetic anti-HER2 immunoliposome was prepared,its physic-chemical characteristics as well as intracellular distribution were evaluated.Twelve nude mice bearing SKBR-3tumor were chosen as experiment animal,which were divided into two groups.Plain and contrast enhanced MR imaging were performed.Paramagnetic anti-HER2 immunoliposome was used as contrast agent for the experimental group and Gadobutrol was used for the control group.The signal intensities on T1 WI in plain MRI and at 10 min,1h,and 6hafter contrast injection were measured respectively.The enhanced rate and contrast-to-noise ratio(CNR)of tumor in the two groups were calculated and compared.Results:The mean diameter,polydisperisity index,zeta potential and r1 relexivity of paramagnetic anti HER2 immunoliposome were 134.2nm,0.29,-32.49 mV and 4.67/mM·s respectively,showing specific binding with high-expressed SK-BR-3breast cancer cells,rhodamine fluorescence was detected intensively in cytoplasm.After paramagnetic anti-HER2 immunoliposome was injected,marked and long-lasted enhancement in tumor tissue could be assessed,the enhanced rate was 121% after 10 min,185% after 1hand 224% after 2hof enhancement.However,in the contrast group,after Gadobutrol as contrast agent was injected,tumor tissue enhanced obviously after 10 min,the enhanced rate was185%,yet the signal intensity decreased 1hafter,which was closed to that as plain MRI.The enhanced rate,CNR of tumor1 hand 6hafter injection of contrast agent in these two groups showed significant statistic difference.Conclusion:Paramagnetic anti-HER2 immunoliposomes show long circulation time,high r1 relaxivity,could be served as a specific target agent for breast cancer.
出处 《放射学实践》 北大核心 2016年第7期586-590,共5页 Radiologic Practice
基金 国家自然科学基金(30700184) 广东省科技计划项目(2013B021800247)
关键词 顺磁性 免疫脂质体 磁共振成像 对比剂 Paramagnetic Immunoliposomes Magnetic resonance imaging Contrast agent
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