Juntao Lang1, Xiaoli Lan2, Yu Liu2, Xueyan Jin2, Tao Wu3, Xun Sun2, Qiong Wen2, Rui An4. 1. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. 2. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China. 3. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China; Department of Nuclear Medicine, The Second People's Hospital of Wuhu, Wuhu 241000, China. 4. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China. Electronic address: anruiwh@163.com.
Abstract
INTRODUCTION: Cancer stem cells (CSCs) are a subpopulation within a tumor, which possesses the characteristics of self-renewal, differentiation, tumorigenicity, and drug resistance. The aim of this study was to target the colorectal CSC marker CD133 with an(131)I-labeled specific monoclonal antibody (AC133 mAb) in a nude mouse xenograft model. METHODS: Colorectal adenocarcinoma cells (LoVo cell line) were separated into CD133(+) and CD133(-) cells by magnetic activated cell sorting. CD133(+), CD133(-), and unsorted LoVo cells were cultured and then implanted subcutaneously into the lower limbs of nude mice (n = 5). AC133 mAb was labeled with (131)I by the iodogen method. RESULTS: The radiolabeled compound, (131)I-AC133 mAb, showed high stability, specificity, and immunoactivity in vitro. Obvious accumulation of (131)I-AC133 mAb was seen in nude mice bearing xenografts of CD133(+) and unsorted LoVo cells, but no uptake was found in mice bearing CD133(-) xenografts or specifically blocked xenografts. Biodistribution analysis showed that the tumor uptake of (131)I-AC133 mAb was 6.97 ± 1.40, 1.35 ± 0.48, 6.12 ± 1.91, and 1.61 ± 0.44% ID/g (n = 4) at day 7 after injection of (131)I-AC133 mAb in CD133(+), CD133(-), unsorted LoVo cell and specifically blocked xenografts, respectively. The results of immunofluorescence, autoradiography, and western blotting further verified the specific binding of (131)I-AC133 mAb to CD133(+) tumors. CONCLUSIONS: This study demonstrates the possibility of targeting CSCs with a radiolabeled AC133 mAb in colorectal cancer xenografts based on in vitro, ex vivo, and in vivo experiments. Our findings suggest a new method for imaging CSCs non-invasively.
INTRODUCTION:Cancer stem cells (CSCs) are a subpopulation within a tumor, which possesses the characteristics of self-renewal, differentiation, tumorigenicity, and drug resistance. The aim of this study was to target the colorectal CSC marker CD133 with an(131)I-labeled specific monoclonal antibody (AC133 mAb) in a nude mouse xenograft model. METHODS:Colorectal adenocarcinoma cells (LoVo cell line) were separated into CD133(+) and CD133(-) cells by magnetic activated cell sorting. CD133(+), CD133(-), and unsorted LoVo cells were cultured and then implanted subcutaneously into the lower limbs of nude mice (n = 5). AC133 mAb was labeled with (131)I by the iodogen method. RESULTS: The radiolabeled compound, (131)I-AC133 mAb, showed high stability, specificity, and immunoactivity in vitro. Obvious accumulation of (131)I-AC133 mAb was seen in nude mice bearing xenografts of CD133(+) and unsorted LoVo cells, but no uptake was found in mice bearing CD133(-) xenografts or specifically blocked xenografts. Biodistribution analysis showed that the tumor uptake of (131)I-AC133 mAb was 6.97 ± 1.40, 1.35 ± 0.48, 6.12 ± 1.91, and 1.61 ± 0.44% ID/g (n = 4) at day 7 after injection of (131)I-AC133 mAb in CD133(+), CD133(-), unsorted LoVo cell and specifically blocked xenografts, respectively. The results of immunofluorescence, autoradiography, and western blotting further verified the specific binding of (131)I-AC133 mAb to CD133(+) tumors. CONCLUSIONS: This study demonstrates the possibility of targeting CSCs with a radiolabeled AC133 mAb in colorectal cancer xenografts based on in vitro, ex vivo, and in vivo experiments. Our findings suggest a new method for imaging CSCs non-invasively.
Authors: Jun Dou; Yaoyao Ni; Xiangfeng He; Di Wu; Miao Li; Songyan Wu; Rong Zhang; Mei Guo; Fengsu Zhao Journal: Am J Transl Res Date: 2016-01-15 Impact factor: 4.060