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.
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.


CONCLUSIONS
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.
Centre de recherche en cancérologie de Nantes-Angers CRCNA, Université de Nantes, INSERM UMR 892, 9 Quai Moncousu, Nantes, France. eric.frampas@chu-nantes.fr
Eric
E
Frampas
Catherine
C
Maurel
Philippe
P
Thedrez
Patricia
P
Remaud-Le Saëc
Alain
A
Faivre-Chauvet
Jacques
J
Barbet
D000818:Animals; D001345:Autoradiography; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology* / Q000378:metabolism*; D007267:Injections; D007553:Isotope Labeling; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D049409:Luciferases, Firefly / Q000235:genetics; D008163:Luminescent Measurements; D051379:Mice; D057054:Molecular Imaging; D011169:Portal Vein; D021381:Protein Transport; D014018:Tissue Distribution
D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D049409:Luciferases, Firefly