二步法预定位技术对荷人肝癌裸鼠模型的MR免疫成像研究  

MR imaging of nude mouse bearing human hepatocellular carcinoma by using two-step pretargeting strategy

作　　者：许乙凯[1] 刘岘[1] 叶靖[1] 

机构地区：[1]第一军医大学南方医院影像中心,广州510515

出　　处：《中华放射学杂志》2005年第4期357-361,共5页Chinese Journal of Radiology

基　　金：国家自然科学基金(30371608);广东省自然科学基金(020053)

摘　　要：目的利用生物素亲和素系统(biotin avidinsystem,BAS)的靶向定位效应和生物放大作用,提高MR分子免疫成像的敏感性。方法制备生物素化抗人肝癌细胞单克隆抗体HAb18并测定其生物素化程度及抗原结合活性。20只荷人肝细胞癌裸鼠分为3组,二步法预定位组8只,先静脉注射生物素化单克隆抗体600μg,24h后再给予钆喷替酸葡甲胺链霉亲和素(Gd DTPA streptavidin,Gd DTPA SA);HAb18单克隆抗体Gd DTPA组6只,经尾静脉注射Gd DTPA HAb18;Gd DTPA对照组6只,静脉注射Gd DTPA。对实验动物行MR扫描,测量SET1WI平扫及增强后10、30、60min及3、6、12、24、48h图像内肿瘤的信号强度,绘制信号强度时间曲线,并计算肿瘤强化率及对比度噪声比(contrast to noiseratio,CNR)。结果HAb18单克隆抗体经生物素化后,每个抗体分子平均可结合20个分子生物素,其抗原结合活性约为91%。二步法预定位组内,肿瘤信号强度缓慢升高,增强后第6小时,肿瘤的强化率、CNR达到最大值,与其他两组相比较差异有统计学意义。48h后,肿瘤的强化仍肉眼可辨。单克隆抗体组内,肿瘤表现为缓慢轻度强化,增强后24h的强化率达13.5%,肿瘤信号强度、CNR与平扫比较差异均有统计学意义(P值均<0.05)。Gd DTPA对照组内,肿瘤表现为快进快出特点的强化特点。结论二步法预定位技?Objective To improve the sensitivity of MR molecular imaging by using targeting and magnifying effects of biotin-avidin system (BAS). Methods After preparing biotinylated monoclonal antibody HAb18, the number of biotin molecules coupled to each antibody and the binding capacity of biotinylated antibody were determined. Two-step pretargeting tumor imaging was first achieved by intravenously injecting biotinylated monoclonal antibody HAb18 into 8 BALB/c nude mice bearing QGY-7723 tumor cells line. 24 h later, Gd-DTAP-streptavidin (Gd-DTPA-SA) was injected. Gd-DTPA-HAb18 and Gd-DTPA were respectively injected intravenously into the other 12 tumor-bearing mice as contrast groups. MR imaging was performed before and 10, 30, 60 min, 3, 6, 12, 24 h, and 48 h after injection of MR contrast agents. All images were obtained using SE T_1-weighted imaging sequence. After MR imaging, enhancement time course of three different groups was determined by using enhancement data measured in the region of interest in the tumor. Enhancement ratio and contrast-to-noise of tumor were also calculated. Results The average number of biotin conjugated with each monoclonal antibody molecular was 20. And the immunoactivity of biotinylated antibody was 91%. In two-step pretargeting strategy, SI of tumor increased slowly and reached the maximum value at 6 h after injection of Gd-DTPA-SA, enhancement ratio and CNR of tumor had significant difference with other two enhancement methods. The enhancing effect of tumor was still perceptible even after 48 h. When using Gd-DTPA-HAb18, the tumor enhancement pattern was slow and slight. Even at 24 h after injection of Gd-DTPA-HAb18, enhancement ratio of tumor was 13.5%. After Gd-DTPA was injected, signal intensity of tumor increased rapidly, and reached the maximum value at 30 min after injection of Gd-DTPA, and then decreased rapidly. Conclusion Two-step pretargeting strategy based on BAS has specific and signal magnifying effects in tumor MR imaging. It can increase the number of gadolinium that bind

关 键 词：预定位技术 二步法 成像研究 裸鼠模型 生物素-亲和素系统 单克隆抗体 HAB18 抗原结合活性 钆喷替酸葡甲胺 强度-时间曲线 DTPA 生物素化 system 信号强度 对比度噪声比 人肝癌细胞 人肝细胞癌 链霉亲和素 尾静脉注射 分子生物素 

分 类 号：R735.7[医药卫生—肿瘤]