靶向ELAM-1磁共振分子探针制备及其靶向性的初步研究  

Preliminary Study on Preparation and Targeting of ELAM-1 Targeted Magnetic Resonance Molecules Probes

作　　者：左志超 董梦莹[1] 邓文娟[1] 王鹏[1] 金观桥[1] 苏丹柯[1] 马婕 李湘茹 刘树英[1] ZUO Zhichao;DONG mengying;DENG Wenjuan;et al(Department of Radiology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province 530021 ,P. R. China)

机构地区：[1]广西医科大学附属肿瘤医院影像诊断中心

出　　处：《临床放射学杂志》2018年第3期530-535,共6页Journal of Clinical Radiology

基　　金：国家自然科学基金(编号:81260334,编号:81460452)

摘　　要：目的制备内皮性白细胞粘附分子-1（ELAM-1）靶向性MR分子探针,分析其表征,并对其体内靶向性进行探讨。方法制备：将羧基修饰过的超小型氧化铁颗粒（USPIO）与ELAM-1的配体唾液酸化酶X（sLeX）进行偶联,再以聚乙二醇（PEG）修饰,制备出靶向ELAM-1的MR分子探针USPIO-sLeX-PEG。表征：分别对USPIO和USPIO-sLeX-PEG进行激光动态光散射、热失重、红外光谱以及弛豫性能测试;靶向效果：分别测量两组荷瘤裸鼠瘤灶注药前后的T_2值,比较USPIO及USPIO-sLeX-PEG在荷瘤裸鼠MR-T_2mapping上的成像效果,扫描完成后对其精细解剖,取组织病理切片行HE染色及免疫组织化学。结果 ELAM-1分子探针USPIO-sLeX-PEG主要表征：USPIO-sLeX-PEG水动力尺寸为（51.82±5.2）nm,聚合物分散指数为（0.233±0.032）;Zeta电位为（-40.17±0.55）mV。USPIO-sLeX-PEG分子探针的纵向率r1及横向弛豫率r2分别为6.1 mM^（-1）·s^（-1）、23.6 mM^（-1）·s^（-1）。靶向效果显示：非靶向性USPIO组与靶向性USPIO-PEG-sLeX组比较,后者的增强扫描T_2值低于前者（P〈0.05）,且后者强化率高于前者（P〈0.05）,即USPIO-PEG-sLeX组荷瘤裸鼠在MR-T_2mapping上具有更好的成像效果。免疫组织化学结果示2组荷瘤裸鼠瘤灶ELAM-1均呈高表达。结论合成的ELAM-1靶向性MR分子探针USPIO-sLeX-PEG表征良好,且对荷瘤裸鼠ELAM-1具有较好的靶向性。Objective To synthesize ELAM-1 targeted MR molecular probe,and verify its targeting efficiency in vivo.Methods Synthesis： USPIO（ ultra small iron oxide particles） modified with carboxyl was coupled to sLeX（ Sialylase X）,which is the ligand of ELAM-1（ endothelial leukocyte adhesion molecule-1）,and then modified with PEG（ polyethylene glycol） to prepare MR molecule probe USPIO-sLeX-PEG that targeting ELAM-1. Characterization： The laser dynamic light scattering,thermogravimetric analysis,infrared spectroscopy,and relaxation performance tests were performed on USPIOsLeX-PEG and USPIO,respectively. Targeting effect： T_2 values of the tumor were measured before and after injection. The imaging effect of USPIO and USPIO-sLeX-PEG for tumor-bearing nude mice on MR-T_2 mapping were compared,after scanning,the tumor-bearing nude mice were subjected to fine anatomy,then histopathological sections were obtained for HE staining and immunohistochemistry. Results The main characterization of USPIO-sLeX-PEG（ molecular probe of ELAM-1） ： The hydrodynamic size of USPIO-sLeX-PEG was（ 51. 82 ± 5. 2） nm,the polymer dispersion index was（ 0. 233 ±0. 032）,and the zeta potential was（-40. 17 ± 0. 55） mv. The longitudinal rate r1 and lateral relaxation rate r2 of USPIO-sLeX-PEG molecular probes were 6. 1 mM^（-1）·s^（-1） and 23. 6 mM^（-1）·s^（-1）,respectively. The targeting efficiency： Compared to non-targeted USPIO group,the target molecular probe USPIO-sLeX-PEG group showed lower T_2 value and higher enhancement rate after injection. That is,the USPIO-PEG-Le X group has a better imaging effect on MR-T_2 mapping.The results of immunohistochemistry showed that ELAM-1 was highly expressed in two groups of tumor-bearing nude mice.Conclusion The synthesized ELAM-1 Targeted MR Molecular Probes USPIO-sLeX-PEG was well characterized,and had a good targeting efficiency for ELAM-1 in tumor-bearing nude mice.

关 键 词：内皮性白细胞粘附分子-1 超小型氧化铁颗粒 超小型氧化铁颗粒-唾液酸化酶X-聚乙二醇 表征靶向性 

分 类 号：R445.2[医药卫生—影像医学与核医学]