Mouse Spontaneous Liver Metastasis Model from Orthotopic Human Colon Cancer Xenograft Stably Expressing Human Sodium-Iodide Symporter Reporter Gene

Subcutaneous human tumor xenografts in immunodeficient mice do not sufficiently represent clinical cancer especially with regard to metastasis. In this study, we therefore developed a mouse spontaneous liver metastasis model from an orthotopic human colon cancer xenograft stably expressing a human sodium-iodide symporter (NIS) reporter gene, of which metastasis can be tracked noninvasively and with 99mTcO4- SPECT or 124I PET. Methods: A recombinant plasmid containing NIS constitutively driven by a cytomegalovirus promoter (pcDNA3-NIS) was transfected into a human colon cancer cell line HCT116, and the stable cell lines were generated. Functional NIS expression in these cells was confirmed by 99mTcO4- uptake assay and Western blotting analysis in vitro. Then, suspensions of the stable cell lines were injected into the cecal walls of nude mice. When the mice developed abdominal masses, the tumors were excised, cut into small pieces, and implanted orthotopically into the cecal walls of different nude mice. Results: Six to eight weeks after the implantation, 99mTcO4- SPECT/CT imaging was performed using a dedicated small animal SPECT/CT system (Gamma Medica-Ideas, Northridge, CA), and focal 99mTcO4- uptakes were detected in the liver. Immunohistochemical analyses of the liver tumors demonstrated NIS expression in the cells, indicating metastases from the NIS expressing orthotopic colon xenografts. Conclusion: We developed a mouse spontaneous liver metastasis model from an orthotopic human colon cancer xenograft, and successfully imaged the metastatic tumors in vivo with 99mTcO4- SPECT. This unique animal model of clinically relevant and externally detectable liver metastases will be useful for studying the mechanism of cancer metastasis and the evaluation of novel anticancer drugs.2011 World Molecular Imaging Congress (WMIC