The Use of Monoclonal Antibodies for Radioscintigraphic Detection of Cancer

Abstract

Beginning with Ehrlich's original “magic bullet” concept of 1904, the pioneering human trials in the late 1970s of Goldenberg and Mach using polyclonal antibodies, and the Nobel Prize-winning work of Kohler and Milstein in 1975 for developing monoclonal antibody (MAb) technology, there has been much interest in the use of antibodies for detecting and treating cancer. Although not the revolutionary breakthrough that was initially hoped for, marked progress has been made. The Food and Drug Administration (FDA) has recently approved the intact murine IgG, 111-indium CYT-103 (satumomoab, Oncoscint™ Cytogen, Princeton, NJ) for clinical use in detecting colorectal and ovarian cancer. However, the agent has been approved for only a single, one-time use, because patients developed an immune response (human anti-mouse antibody, or HAMA) that alters MAb biodistribution and may limit the clinical effectiveness of this agent when repeat studies are performed. Other MAbs reacting with a variety of antigens and targeting numerous tumors, including breast, lung, prostate, and melanomas, are currently undergoing large-scale clinical trials. To reduce induction of immune responses, many of the agents use immunoglobulin fragments [Fab, or F(ab)2] labeled with the short-lived isotope 99m-technetium used for most routine nuclear medicine diagnostic testing. Future developments will use even smaller fragments such as single chain antibodies or custom synthesized molecular recognition units (small peptides containing only the specific antigen combining site). Presented herein is an overview of the past results and an assessment of the current status of radioimmunoscintigraphy for various neoplasms.