Status of Radioimmunotherapy in the New Millennium

This synopsis attempts to summarize progress made in radioimmunotherapy (RIT) by the end of the 20^th century addressing the problems, possible solutions, and recent developments. The reduction of minimal residual disease in an adjuvant setting appears to be a feasible goal for RIT utilizing short-range alpha-emitters. RIT has been more successful in the radiosensitive hematologic malignancies, for example lymphomas and leukemias as compared with small solid tumors. Several radiopharmaceuticals seem near approval for RIT in patients with non-Hodgkin's lymphoma (NHL) as therapeutic responses, including complete responses, are common. Obstacles to successful RIT have been recognized and strategies to overcome these hurdles and to improve efficacy are continuously being developed resulting in encouraging outcome particularly with locoregional routes of administration in solid tumors. Systemic RIT for solid tumors will need manipulating the tumor-host to improve the tumor uptake and retention of radioimmunoconjugates (RICs). The utilization of radiometals, stable chelators, biodegradable linkers and bone marrow transplantation should be able to deliver the radiation dose required for successful treatment. In conjunction with additional synergistic agents, RIT is likely to have a great impact on the treatment of solid tumors. The ability to generate new constructs, such as bivalent antibodies or fusion proteins incorporating two different functional proteins opens exciting opportunities for new therapeutic modalities. These developments will hopefully offset the impediments to the successful use of RIT.