title: Targeting cancer stem cells with an 131I-labeled anti-AC133 monoclonal antibody in human colorectal cancer xenografts.
abstract: BACKGROUND
  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: 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.
authors: Juntao
authors: J
authors: Lang
authors: 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.
authors: Xiaoli
authors: X
authors: Lan
authors: 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.
authors: Yu
authors: Y
authors: Liu
authors: 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.
authors: Xueyan
authors: X
authors: Jin
authors: 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.
authors: Tao
authors: T
authors: Wu
authors: 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.
authors: Xun
authors: X
authors: Sun
authors: 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.
authors: Qiong
authors: Q
authors: Wen
authors: 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.
authors: Rui
authors: R
authors: An
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D015703:Antigens, CD / Q000276:immunology*; D001345:Autoradiography; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000000981:diagnostic imaging*; D010455:Peptides / Q000276:immunology*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D000071916:AC133 Antigen; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse
keywords: cancer stem cells; monoclonal antibody; radioimmunoimaging; single positron emission computed tomography (SPECT)