Immunohistochemical antigenic expression and in vivo tumor uptake of monoclonal antibodies with specificity for tumors of the gastrointestinal tract.

Abstract

Two monoclonal antibodies with specificity for carcinoembryonic antigen and Ca 19-9 gastrointestinal tract tumor associated antigens were infused after iodination with 125I and 131I, respectively, in six patients 3 days and in one patient 4 days before radical surgery for colon or rectal carcinoma. Biopsy specimens from tumor, normal colon, fat, muscle, and skin along with a blood sample were excised at surgery and counting was performed for gamma emission. Fragments were then studied by two independent pathologists for immunohistochemical expression of corresponding antigens using the avidin-biotin peroxidase complex. A correlation study was thereafter performed between the amount of antibody bound in vivo, expressed as the percentage of injected dose per gram of tissue and the quantitative expression of tumor associated antigens, taking into account both the percentage of cells expressing the antigen and intensity of staining. For this limited number of patients a good correlation was found between amount of targeted antibodies and amount of expressed antigens. For carcinoembryonic antigen, r values were 0.69 and 0.90 for each pathologist (with an r value of interobserver correlation of 0.74); for Ca 19-9, values of 0.78 and 0.84 were obtained for each observer, with an interobserver r value of 0.97. Based on this limited study, it may be assumed that the possibility of imaging a given tumor is in part correlated to intensity of antigenic expression at the tumor site; other parameters, like tumor vascularization and blood flow for instance, are, however, to be considered for accessibility of antibodies to corresponding antigens.