Radioimmunodetection of cancer with monoclonal antibodies: current status, problems, and future directions

Early studies of immunoscintography with affinity-purified 131I-labeled polyclonal antibodies reactive against oncofetal antigens such as carcinoembryonic antigen (CEA) were moderately successful in detecting metastatic colorectal carcinoma. However, because of low tumor to background ratios of isotope, background subtraction techniques using 99Tc-labeled albumin were required to visualize small lesions. Antisera were often of low titer and lacked specificity. These problems could be overcome for the most part following the development of highly specific monoclonal antibodies (MoAb) against a variety of tumor-associated antigens. A number of clinical trials using 131I- or 111In-labeled MoAb to image tumors have demonstrated successful localization without the use of subtraction techniques. Variables limiting the usefulness of murine MoAb for diagnosis have included increased localization in liver and spleen, tumor vascularity and heterogeneity of antigen expression, and development of human antimurine globulins. Methods to overcome some of these problems are discussed. Radiolabeled MoAb appear useful as an adjunct to conventional diagnostic techniques both as a means to predict which antibodies might be useful for treatment and, in select patients, as a basis for treatment decisions.