Radioimmunoscintigraphy: A Clinical Perspective

The use of radiolabeled antibodies for tumor localization was first suggested by Pressman and Korngold in 1953 (I). The initial human imaging studies with polyclonal antibodies met with limited success (2). Although some investigators have reported excellent sensitivity (3) for tumor detection with polyclonal antibodies, the image quality has been marginal and the results have not been reproducible (4-6). In 1975, Kohler and Milstein succeeded in creating an immortal cell (hybridoma) capable of producing an antibody of predetermined specificity in unlimited quantities (7). To produce the hybridoma, mice are immunized with tumor cells, i.e., antigens. The mouse immune system responds to these foreign antigens and antitumor antibodies are produced by their lymphocytes. The spleen is excised and minced in order to obtain a single cell suspension of lymphocytes. Lymphocytes can survive but cannot grow in cell culture. These lymphocytes are harvested and then mixed with mouse myeloma cells. The mouse myeloma cells, which are derived from a mouse cancer, are "immortal" and in addition have been selected for an enzyme deficiency (hypoxanthine phosphoribosyl transferase). When these enzyme-deficient cells are grown in special media (HAT media) the myeloma cannot produce the necessary nutrients to survive and will die out. A fusing agent is added to the mixture of lymphocytes and myeloma cells and three cell populations-result: 1) the unfused lymphocytes, which cannot grow in culture; 2) the unfused myeloma cells, which cannot grow in HAT media; and 3) the fused cells, i.e., hybridoma that have complimentary characteristics from each cell and that can grow in culture producing large amounts of antibodies. The fusion product (hybridoma) of a single antibody forming cell and a tumor cell will have the ability to secrete a single species of antibody, and the immortality to enable it to proliferate continuously. This provides an unending supply of antibody with a single preselected specificity (Fig. 1). Monoclonal antibody (MoAb) technology has led to the discovery of a host of tumor-associated antigens on human tumors and to the production of a large amount of well-characterized,