F4/80 MR分子靶向成像用于结肠癌巨噬细胞的活体检测

F4/80-targeted MR molecular imaging in mice with colon cancer: in vivo MR detection of tumor-associated macrophages

目的应用巨噬细胞特异性表面抗原F4/80靶向对比剂F4/80-USPIO显示结肠癌动物模型中的肿瘤相关巨噬细胞。方法构建结肠癌皮下移植瘤动物模型。通过免疫组化染色实验,显示F4/80在结肠癌组织内的表达率。测定USPIO及F4/80-USPIO的基本理化特性,比较两者的T_2弛豫率。对荷瘤小鼠行MRI扫描,测量注射F4/80-USPIO前、后肿瘤的T_2信号强度值变化。结果 F4/80-USPIO的粒径约49.81nm,弛豫率为0.0384mM^(-1)s^(-1),高于USPIO;免疫组化染色实验显示结肠癌组织内有大片区域F4/80受体阳性表达;小鼠结肠癌皮下移植瘤模型MR活体成像示F4/80-USPIO降低了瘤灶的T_2信号。结论结肠癌动物模型中的肿瘤相关巨噬细胞可特异性摄取F4/80-USPIO,F4/80-USPIO可作为结肠癌T_2阴性对比剂。

Objective To detect tumor-associated macrophages (TAMs) in mice with colon cancer using a targeted USPIO contrast agent F4/80-USPIO. Methods A subcutaneous transplantation tumor model of human colon cancer was established using mice. The expression rate of F4/80 in colon cancer tissues was detected by incubating F4/80 antibodies with colon cancer tissue sections. The physicochemical properties of F4/80-USPIO and USPIO were determined, and T 2 relaxation rates of them were compared. MR axial T 2WI plain scan and enhanced scan were performed respectively in the tumor bearing mice. Measurement of T 2 signal intensity changes were performed respectively before and after injection of F4/80-USPIO. Results The experimental results showed that the USPIO conjugated with F4/80 had a particle size of approximately 49.81 nm, with a high relaxation rate (R2) of 0.0384 mM -1 s -1 . Immunohistochemistry confirmed binding characteristics of F4/80 antibodies to macrophages, in other words, F4/80-USPIO can be specifically uptaken by macrophages. Vivo serial MR imaging of subcutaneous transplantation tumor model of colon cancer showed low signal intensity on T 2WI caused by F4/80-USPIO. Conclusion F4/80-USPIO can be specifically uptaken by macrophages of subcutaneous transplantation tumor model. It was confirmed that F4/80-USPIO can be used as T 2 contrast agent in colon cancer.