Advancing role of radiolabeled antibodies in the therapy of cancer.

Abstract

This review focuses on the use of radiolabeled antibodies in the therapy of cancer, termed radioimmunotherapy (RAIT). Basic problems concerned with the choice of antibody, radionuclide, and physiology of the tumor and host are discussed, followed by a review of the pertinent clinical publications of various radioantibody constructs in the treatment of hematopoietic and solid tumors of diverse histopathology, grade, and stage, and in different clinical settings. Factors such as dose rate delivered, tumor size, and radiosensitivity play a major role in determining therapeutic response, while target-to-nontarget ratios and, particularly, circulating radioactivity to the bone marrow determine the principal dose-limiting toxicities. RAIT appears to be gaining a place in the therapy of hematopoietic neoplasms, such as non-Hodgkin's lymphoma: several agents are advancing in clinical trials toward registration, and one has recently been approved by the FDA. Although RAIT of solid tumors has shown less progress, use of pretargeting strategies, such as an affinity-enhancement system consisting of bispecific antibodies separating targeting from delivery of the radiotherapeutic, appears to enhance tumor-to-nontumor ratios, and may increase radiation doses to tumors more selectively than directly labeled antibodies.