The intraportal injection model for liver metastasis
| Autor: | Eric Frampas, Philippe Thedrez, Patricia Remaud-Le Saëc, Alain Faivre-Chauvet, Jacques Barbet, Catherine Maurel |
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| Rok vydání: | 2011 |
| Předmět: |
Pathology
medicine.medical_specialty Colorectal cancer medicine.medical_treatment Injections Metastasis Mice Carcinoembryonic antigen Luciferases Firefly Cell Line Tumor Adjuvant therapy Animals Humans Medicine Tissue Distribution Radiology Nuclear Medicine and imaging Immunoglobulin Fragments biology Portal Vein business.industry Liver Neoplasms General Medicine medicine.disease Tumor antigen Carcinoembryonic Antigen Molecular Imaging Disease Models Animal Protein Transport Isotope Labeling Radioimmunotherapy Luminescent Measurements biology.protein Autoradiography Female Anti-Carcinoembryonic Antigen Antibody Antibody Colorectal Neoplasms business |
| Zdroj: | Nuclear Medicine Communications. 32:147-154 |
| ISSN: | 0143-3636 |
| DOI: | 10.1097/mnm.0b013e328341b268 |
| Popis: | 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 (1×106) 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 1×106 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. |
| Databáze: | OpenAIRE |
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