生物素-亲和素系统在MR靶向成像中的应用

目的：探讨利用生物素-亲和素系统的靶向定位效应和生物放大作用，提高MR分子成像的敏感性。方法：制备生物素化HAb18单克隆抗体并测定其生物素化程度及抗原结合活性。将8只荷人肝细胞癌裸鼠静脉注射生物素化单克隆抗体600μg，24h后腹腔注射80μg亲和素，30min后再静脉给予Gd-DTPA-链霉亲和素。对实验动物行MR扫描，测量SET1WI平扫及增强后10、30min及2、6、12、24h图像内肿瘤、肝脏、肌肉的信号强度，绘制信号强度-时间曲线，并计算其强化率及对比度噪声比。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％。增强后肿瘤信号强度缓慢升高．在注射对比剂后第6小时，肿瘤的强化率、比度噪声比达到最大值，与其他各时间点有显著性差异。肝脏在注射对比剂后第6小时的信号强度达到最高，而后信号强度下降．增强后12h的信号强度与平扫相似。肌肉表现为轻度强化，增强后各时间点的信号强度与平扫相比无明显差异。结论：利用生物素．亲和素技术对肿瘤进行MR靶向成像，具有特异性强化作用并能延长肿瘤的强化时间．但Gd—DTPA—SA的血池效应也造成了肝脏的持续强化。

Application of biotin-avidin system in targeted magnetic resonance imaging]

OBJECTIVE: To improve the sensitivity of magnetic resonance molecular(MR) imaging on the basis of the targeting and magnifying effects of biotin-avidin system. METHODS: Biotinylated monoclonal antibody HAb18 was prepared, and the number of biotin molecules coupled to each antibody molecule was assayed together with the binding capacity of the biotinylated antibody. HAb18 was intravenously injected into 8 BALB/c nude mice bearing QGY-7723 tumor cells, followed by administration of 80 microg avidin as the chaser 24 h later and then Gd-DTAP-streptavidin injection after another 30 min. MR imaging was performed before and 10, 30, 60 min and 3, 6, 12, and 24 h after the injection of the contrast agents. All the images were obtained using SE T(1)-weighted imaging sequence. The enhancement time course of the tumor, liver and muscles were determined by measuring the signal intensity (SI) in the region of interest in the tumor, and the enhancement ratio and contrast-to-noise ratio (CNR) of the tumor also calculated. RESULTS: On average, 20 biotin molecules conjugated with each monoclonal antibody molecule, and the immunoactivity of the biotinylated antibody reached 91%. The SI of the tumor increased slowly and peaked at 6 h after injection of Gd-DTPA-streptavidin, when the enhancement ratio and CNR of the tumor were significantly higher then those measured on other time points. The SI of the liver reached the maximum value at 6 h after injection of the contrast agent, and then declined to the non-enhanced level 12 h after injection. The SI of the muscle exhibited no significant difference after enhancement. CONCLUSIONS: In targeted MR of the tumor, biotin-avidin system produces specific and prolonged enhancement of the signals, but blood pool effect of Gd-DTPA-streptavidin also causes prolonged enhancement of the liver.