The intraportal injection model for liver metastasis: advantages of associated bioluminescence to assess tumor growth and influences on tumor uptake of radiolabeled anti-carcinoembryonic antigen antibody

BACKGROUNDRadioimmunotherapy is emerging as a new tool for adjuvant therapy of colorectal cancer. The liver remains the main site for metastases, carrying a high mortality rate. Many animal models are available but none associates easy, reliable implantation and in-vivo follow-up for experimental therapeutic studies. The aims of this study were to develop a reliable hepatic metastatic colonic cancer model in mice using the intraportal route for injection, with follow-up by bioluminescence (BLI) and to evaluate the impact of tumor location on tumor antigen direct targeting using radiolabeled anti-CEA (carcinoembryonic antigen) antibodies. METHODSLs-174T Luc+ is a colon carcinoma cell line strongly expressing CEA, transfected with the luciferase gene for BLI. Isolated or aggregated cells (1×10) were injected through the portal vein. The tumor burden was investigated using BLI to assess hepatic implantation and growth kinetics. The biodistribution of the I anti-CEA antibody fragment (F6) was studied in this model and was compared with subcutaneous implantation. RESULTSThe tumor implantation rate was 100% using aggregated cells compared with 26.6% of isolated cells. Photons emitted by 1×10 cells were detected by BLI immediately after injection and allowed visual confirmation of hepatic distribution. The tumor growth was assessed over time to select homogeneous groups of animals. Radiolabeled anti-CEA antibody biodistributions showed a significantly higher uptake in hepatic than in subcutaneous tumors. CONCLUSIONThe association of hepatic tumor graft through the portal route and BLI provides a reliable animal model and permits sensitive in-vivo detection and follow-up of hepatic metastases. The hepatic model seems to more closely reproduce colon cancer metastases compared with subcutaneous metastasis. The hepatic model is of particular interest for studying radioimmunotherapy.