title: Carcinoembryonic antigen expression, antibody localisation and immunophotodetection of human colon cancer liver metastases in nude mice: a model for radioimmunotherapy.
abstract: 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.
authors: Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors: C A
authors: CA
authors: Vogel
authors: M C
authors: MC
authors: Galmiche
authors: P
authors: P
authors: Westermann
authors: L Q
authors: LQ
authors: Sun
authors: A
authors: A
authors: Pèlegrin
authors: S
authors: S
authors: Folli
authors: A
authors: A
authors: Bischof Delaloye
authors: D O
authors: DO
authors: Slosman
authors: J P
authors: JP
authors: Mach
authors: F
authors: F
authors: Buchegger
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D002232:Carbocyanines; D002272:Carcinoembryonic Antigen / Q000032:analysis*; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology*; D005453:Fluorescence; D005456:Fluorescent Dyes; D005677:G(M1) Ganglioside / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008113:Liver Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D014407:Tumor Cells, Cultured; D014916:Whole-Body Irradiation
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D002232:Carbocyanines; D002272:Carcinoembryonic Antigen; D005456:Fluorescent Dyes; C085321:cyanine dye 5; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside