I. CLINICAL ASPECTS OF RADIOIMMUNOTHERAPY A. Antibodies The development of radiolabeled antibodies that bind to tumor-associated antigens for effective radioimmunotherapy (RIT) of malignancy has been very challenging (1-4). Although murine antibodies have been the most widely used for RIT studies, the problems related to immunogenicity have resulted in numerous modifications involving the reengineering of antibodies. One of the simplest approaches has been enzymatic cleavage to form fragments. They generally have more utility for imaging than RIT because of lower tumor uptake, whereas products from recombinant DNA technology have resulted in a variety of types of constructs with applicability to RIT. Advantages of more humanized constructs (mouse-human chimeric, complementarity-determining region-grafted, minibodies) include less immunogenicity, which may allow for repeated dosing, longer effective half-life, which may produce a higher uptake and radiation absorbed dose in tumor, and the potential for larger amounts of antibody to be tolerated without adverse effects. The technologic advancements have allowed for the development of constructs that are not only humanized but may have specific binding sites for a radiolabel, drug, toxin, or effector function.