Tumor targeting with radiolabeled antibodies in a human carcinoembryonic antigen transgenic mouse model.
Mice transgenic for the carcinoembryonic (CEA) gene were used to study the biodistribution and tumor targeting of a radioiodinated monoclonal antibody (MAb), T84.66. The specificity of antibody uptake in tumors was assessed in mice bearing a CEA-transfected syngeneic tumor as well as the antigen-negative parental tumor. With high CEA-expressing tumors, the percent injected dose per gram (%ID/g) approached 30% at 48 hr. Tumor uptake in antigen-positive tumors was 5-8-fold higher than that observed in the antigen-negative parental tumors. Only antigen-positive tumors were visualized by immunoscintigraphy. The tumor targeting obtained in athymic nude mice bearing human tumor xenografts was similar to that observed with CEA-expressing murine tumors implanted in either athymic nude or transgenic mice. The degree of localization of CEA-transfected murine tumors was related with the level of antigen expression. Circulating antigen-radio-antibody complexes were not detected while blood clearance of radio-antibody was similar between transgenic and non-transgenic mice. With the exception of the large bowel, the distribution of radioiodinated MAb in normal tissues was similar in both CEA transgenic and non-transgenic mice. Increased localization of intact antibody was observed in the large bowel from transgenic mice, suggesting specific targeting to antigen-positive normal tissues. These results suggest that the CEA transgenic mouse model will be useful in the development of antibodies for radio-immunodetection and treatment of carcinomas expressing CEA.
Szalai
G
G
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
Williams
L E
LE
Primus
F J
FJ
D000818:Animals; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D004195:Disease Models, Animal; D005260:Female; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection; D019275:Radiopharmaceuticals; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals