Review of clinical radioimmunotherapy.

Radioimmunotherapy involves a form of biologically targeted radiopharmaceutical treatment in which a radioactive isotope (typically a short-range, high-energy beta-emitter) is chemically bound to a target-specific monoclonal antibody or fragment. Thus, these radioimmunoconjugates combine the exquisite targeting specificity of the humoral immune system with the known cancer-killing power of high-energy radiotherapy. To date, two radioimmunotherapy agents have been fully approved for commercial use: 90Yttrium ibritumomab tiuxetan and (131)Iodine tositumomab. Both compounds target the CD20 surface molecule found on normal and malignant B cells, and both are medically indicated for the treatment of indolent B-cell lymphoma and related conditions. Clinical results are excellent (20-40% complete response rates and 60-80% overall response rates) and toxicity is typically quite mild. Current research is now attempting to both explore the biology of these compounds and to expand the spectrum of CD20+ diseases that could be treated using either or both of these active agents. Concurrently, work is in progress to achieve the same excellent clinical results using antibodies specific for other, more common epithelial tumors. This work is at an earlier stage than the lymphoma work, partly due to the high innate radiosensitivity of the lymphoid system. Thus, various enhancement methodologies are being explored to increase clinical response rates for these solid tumors, and a number of solid tumor RIT agents are now in early-stage clinical trials. The most likely pattern of use for this field in the next 5 years will probably involve combination or sequential regimens incorporating both radioimmunotherapy and more conventional chemotherapy or external radiotherapy.