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Tumor targeting with radiolabeled antibodies in a human carcinoembryonic antigen transgenic mouse model
Author(s) -
Szalai György,
Williams Lawrence E.,
Primus F. James
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000315)85:6<751::aid-ijc2>3.0.co;2-8
Subject(s) - carcinoembryonic antigen , antibody , antigen , genetically modified mouse , transgene , biodistribution , monoclonal antibody , immunoscintigraphy , pathology , microbiology and biotechnology , biology , cancer research , medicine , cancer , immunology , radioimmunotherapy , in vivo , gene , biochemistry
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. Int. J. Cancer 85:751–756, 2000. © 2000 Wiley‐Liss, Inc.