对比剂Gd-DTPA-BSA-chTNT的研制及其在乳腺癌裸鼠模型活体MR分子成像中的应用  

Development of a new specific MR contrast agent Gd-DTPA-BSA-chTNT and its application in vivo molecular MR imaging in the nude mouse model implanted with human breast cancer

作　　者：龚英[1] 汪登斌[1] 钟高仁[2] 

机构地区：[1]上海交通大学医学院附属瑞金医院放射科 [2]复旦大学药学院放射药学教研室,上海200032

出　　处：《诊断学理论与实践》2007年第1期30-35,共6页Journal of Diagnostics Concepts & Practice

基　　金：国家自然科学基金(30370428);上海市基础研究重点项目(04JC14047)

摘　　要：目的:探索采用特异性对比剂进行乳腺癌模型活体MR分子成像的可能性,及其在诊断乳腺癌方面的价值。方法:在一定条件下将Gd-DTPA-BSA与单克隆抗体chTNT反应生成MR特异性对比剂Gd-DTPA-BSA-chTNT。在5周龄雌性、无特定病原体(SPF级)BALB/c裸小鼠原位接种人乳腺癌细胞(MDA-MB-231)制作动物模型。将12只人乳腺癌裸鼠随机分为实验组和对照组,前者注射Gd-DTPA-BSA-chTNT,后者注射含相同Gd离子浓度的Gd-DTPA,两者均经尾静脉注射,注射剂量均为0．2 ml/只。测量SE T1WI平扫及引入对比剂5 min及1、2、3、4、8、12、24 h后的肿瘤信号强度,并计算对比度噪声比(CNR)。将右侧前肢肌肉组织信号变化作为参照物,并进行统计学分析。结果:实验组注射对比剂Gd-DTPA-BSA-chTNT后1 h裸鼠瘤体信号强度开始升高,于4 h达到高峰,且延迟24 h后信号强度仍有增高,与注射对比剂前比较差异有统计学意义(P＜0．001)。但裸鼠肌肉信号始终无明显升高,与注射对比剂前比较无显著差异(P＞0．05)。对照组注射对比剂Gd-DTPA后5 min及1、2、3、4 h裸鼠瘤体及肌肉信号变化与注射对比剂前比较,差异有统计学意义(P＜0．001);本组8 h后成像显示对比剂退出,与对比剂注射前比较无统计学意义(P＞0．05)。结论:MR特异性对比剂Gd-DTPA-BSA-chTNT,对乳腺癌(MDA-MB-231)裸鼠模型肿瘤灶有较好的特异性和靶向作用,可用于乳腺癌模型活体MR分子成像研究,并将有利于乳腺癌病灶的检出及定性诊断。Objective To explore the possibility of in vivo molecular imaging with MR in the nude mouse model implanted with breast cancer using specific contrast agents, and to evaluate the diagnostic value for breast cancer. Methods The specific contrast agent Gd-DTPA-BSA-chTNT was obtained by conjugating Gd-DTPA-BSA and monoclonal antibody of chTNT under specific conditions. The breast cancer cells of MDA-MB-231 were orthotopically implanted in the five-week-old BALB/c female nude mice（class SPF） to establish the animal model. Twelve nude mice with human breast cancer were randomly divided into the experimental group （n=6） and the control group （n=6）. The animals in the experimental group were injected with Gd-DTPA-BSA-chTNT via vena caudalis, whereas the routine Gd-DTPA was used in the control group at the same dosage of gadolinium with the same amount of 0.2 ml as the experimental group. The tumor signal intensities （SI） on T1WI were measured at 5 min, 1 h, 2 h, 3h, 4 h, 8 h, 12 h and 24 h respectively after injection of contrast agents with the SI of the anterior limb muscles on the same side as control, and then all of the results were statistically analyzed. The CNR （contrast to noise ratio） was calculated as well. Results The tumor SI increased remarkably in the experimental group at 1 hour after injection of Gd-DTPA-BSA-chTNT, reached the peak at 4 h, and enhanced persistently for more than 24 h. There was a statistical difference on the SI in the experimental group before and after injection of the specific contrast agents （P〈0.001）. The SI of the muscles did not increased obviously in all the time and no statistical difference between precontrast and postcontrast imaging （P〉0.05）. In comparison with the precontrast imaging, the SI of tumor and muscles in the control group increased greatly at 5 min, 1 h, 2 h, 3 h and 4 h respectively after injection of Gd-DTPA with significant difference （P〈0.001） between the images with and without contrast. And the contrast in the tumors al

关 键 词：裸鼠模型 单克隆抗体 对比剂 磁共振成像 乳腺癌 活体分子成像 

分 类 号：R730.44[医药卫生—肿瘤]