BACKGROUND: Radioimmunotherapy 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. METHODS: Ls-174T Luc+ is a colon carcinoma cell line strongly expressing CEA, transfected with the luciferase gene for BLI. Isolated or aggregated cells (1×10(6)) were injected through the portal vein. The tumor burden was investigated using BLI to assess hepatic implantation and growth kinetics. The biodistribution of the 125I anti-CEA antibody fragment (F6) was studied in this model and was compared with subcutaneous implantation. RESULTS: The tumor implantation rate was 100% using aggregated cells compared with 26.6% of isolated cells. Photons emitted by 1×10(6) 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. CONCLUSION: The 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.
BACKGROUND: Radioimmunotherapy 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. METHODS: Ls-174T Luc+ is a colon carcinoma cell line strongly expressing CEA, transfected with the luciferase gene for BLI. Isolated or aggregated cells (1×10(6)) were injected through the portal vein. The tumor burden was investigated using BLI to assess hepatic implantation and growth kinetics. The biodistribution of the 125I anti-CEA antibody fragment (F6) was studied in this model and was compared with subcutaneous implantation. RESULTS: The tumor implantation rate was 100% using aggregated cells compared with 26.6% of isolated cells. Photons emitted by 1×10(6) 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. CONCLUSION: The 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.
Authors: Xiaoyan Liang; Michael E De Vera; William J Buchser; Antonio Romo de Vivar Chavez; Patricia Loughran; Donna Beer Stolz; Per Basse; Tao Wang; Bennett Van Houten; Herbert J Zeh; Michael T Lotze Journal: Cancer Res Date: 2012-04-03 Impact factor: 12.701
Authors: Eric Frampas; Catherine Maurel; Patricia Remaud-Le Saëc; Thibault Mauxion; Alain Faivre-Chauvet; François Davodeau; David M Goldenberg; Manuel Bardiès; Jacques Barbet Journal: Eur J Nucl Med Mol Imaging Date: 2011-08-20 Impact factor: 9.236