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.
Copyright 2000 Wiley-Liss, Inc.