F4/80 MR分子靶向成像用于结肠癌巨噬细胞的活体检测
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摘要
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.
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.
引文
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[2] Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy [J]. Immunity, 2014, 41(1): 49-61.
[3] Qian BZ, Pollard W. Macrophage diversity enhances tumor progression and metastasis[J]. Cell, 2010, 141(1): 39-51.
[4] Biswas SK, Allavena P, Mantovani A. Tumor-associated macrophages: functional diversity,clinical significance,and open questions [J]. Semin Immunopathol, 2013, 35(5): 585-600.
[5] 王芳, 陆菁菁,金征宇.新型磁共振对比剂USPIO及应用研究现状[J]. 国际医学放射学杂志, 2008,31(5): 372-375.
[6] 王勤. CXCR4结合多肽标记超微超顺磁性纳米氧化铁颗粒在裸鼠胰腺癌模型中的在体磁共振成像研究[D].北京:北京协和医学院, 2013, 20-59.
[7] 王琳琳,于德新,杨传红,等. VEGF-C靶向USPIO在大鼠肝癌特异性MR成像中的价值[J]. 实用放射学杂志, 2014,29(8): 1392-1395.
[8] Linker RA, Kroner A, Horn T, et al. Iron particle-enhanced visualization of inflammatory central nervous system lesions by high resolution: preliminary data in an animal model [J]. AJNR, 2006, 27(6): 1225-1229.
[9] Lin RY, Dayananda K, Chen TJ, et al. Targeted RGD nanoparticles for highly sensitive in vivo integrin receptor imaging [J]. Contrast Media Mol Imaging, 2012, 7(1): 7-18.
[10] 黄艺婧,刘赛,徐平,等.检测BDV抗原的双抗夹心ELISA法的建立[J].免疫学杂志,2013,29(5):428-431.
[11] 谭延斌.不同材料包被的SPIO对巨噬细胞的生物学影响及磁共振成像效应[D].杭州:浙江大学,2010.13-16.
[12] LM, TP, A W. Cell tagging with clinically approved iron oxides: feasibility and effect of lipofection,particle size, and surface coating on labeling efficiency [J]. Radiology, 2005, 235(1): 155-161.
[13] G B, F J,N B. Macrophage imaging by USPIO-enhanced MR for the differentiation of infectious osteomyelitis and aseptic vertebral inflammation [J]. Eur Radiol, 2009, 7(19): 1604-1611.