Targeting cancer stem cells with an I-131-labeled anti-AC133 monoclonal antibody in human colorectal cancer xenografts

摘要

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 I-131-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 I-131 by the iodogen method. Results: The radiolabeled compound, I-131-AC133 mAb, showed high stability, specificity, and immunoactivity in vitro. Obvious accumulation of I-131-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 I-131-AC133 mAb was 6.97 +/- 1.40, 135 +/- 0.48, 6.12 +/- 1.91, and 1.61 +/- 0.44% ID/g (n = 4) at day 7 after injection of I-131-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 I-131-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. (C) 2015 Elsevier Inc. All rights reserved.