Carcinoembryonic antigen expression, antibody localisation and immunophotodetection of human colon cancer liver metastases in nude mice: a model for radioimmunotherapy.
Data(s) |
1996
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Resumo |
Colorectal cancer frequently disseminates through the portal vein into the liver. In this study, outbred Swiss nude mice were adapted to facilitate the induction of liver metastases by a pre-grafting treatment with 6 Gy total body irradiation and i.v. injection of anti-asialo GM1 antibody. One day later, cultured LS 174T human colon cancer cells were injected into the surgically exposed spleen, which was resected 3 min later. In 48 of 65 mice, a few to several hundred liver metastases were macroscopically observed at dissection 3 to 4 weeks after transplantation. Ten of 10 mice, followed-up for survival, died with multiple large confluent liver metastases. By reducing the radiation dose to 4 or 0 Gy, or omitting the anti-asialo GM1 antibody injection, only 60%, 37% or 50% of mice, respectively, had visible metastases 3 weeks after transplantation. Carcinoembryonic antigen (CEA) measured in tumour extracts was in the mean 25.6 micrograms/g in liver metastases compared with 9.2 micrograms/g in s.c. tumours. Uptake of radiolabelled anti-CEA monoclonal antibody (MAb) in the metastases 12, 24 and 48 hr after injection gave a mean value of 39% of the injected dose per gram of tissue (ID/g). In comparison, MAb uptake in s.c. and intrasplenic tumours or lung metastases gave a mean percentage ID/g of 20, 18 and 15, respectively. Laser-induced fluorescence after injection of indocyanin-MAb conjugate allowed direct visual detection of small liver metastases, including some that were not visible under normal light. Preliminary results showed that mice, pre-treated with 4 Gy irradiation and the anti-asialo GM1 injection, were tolerant to radioimmunotherapy with a total dose of 500 muCi 131I labeled anti-CEA intact MAbs given in 3 injections. |
Identificador |
http://serval.unil.ch/?id=serval:BIB_EDED82725C81 isbn:0020-7136 (Print) pmid:8760602 doi:10.1002/(SICI)1097-0215(19960717)67:2<294::AID-IJC23>3.0.CO;2-A isiid:A1996UZ63900023 |
Idioma(s) |
en |
Fonte |
International Journal of Cancer, vol. 67, no. 2, pp. 294-302 |
Palavras-Chave | #Animals; Antibodies/pharmacology; Antibodies, Monoclonal; Carbocyanines; Carcinoembryonic Antigen/analysis; Colonic Neoplasms/immunology; Colonic Neoplasms/pathology; Fluorescence; Fluorescent Dyes; G(M1) Ganglioside/immunology; Humans; Immunohistochemistry; Lasers; Liver Neoplasms/pathology; Liver Neoplasms/radiotherapy; Mice; Mice, Nude; Neoplasm Transplantation; Radioimmunotherapy; Tumor Cells, Cultured; Whole-Body Irradiation |
Tipo |
info:eu-repo/semantics/article article |