Summary

As with chemotherapy, RIT has had its initial successes in the hematologic neoplasms. Two radiolabeled antibodies have been approved by the FDA—one labeled with 90Y, the other with 131I, both against the CD20 receptor present in most B-cell lymphomas. Significant response rate and duration improvements with these agents, both in the myeloablative and nonmyeloablative setting, have led to a resurgence of interest in RIT. Effective RIT of solid tumors is however far from FDA approval, with no agents currently in phase 3 trials.

Unlike B-cell lymphoma, where the host human does not readily mount an immune response against xenogeneic protein, solid tumor RIT cannot be undertaken with murine antibodies, and the clearance kinetics of less immunogenic chimeric and humanized antibodies probably do not allow the delivery of large-enough amounts of radiation to tumor, even at myeloablative doses. Humanized intact immunoglobulins have been approved for a variety of solid tumors, including breast and colon cancer; radiolabeled antibodies have however not shown great promise in solid tumors. This has spurred the development of antigen-binding constructs and other strategies, including multistep targeting to increase relative tumor radiation-absorbed dose.

Genetic engineering has provided not only smaller proteins, for example, single-chain fragments, but also bispecific antibodies that can attach to tumor cells and provide a site for attachment of radionuclide-carrying molecules. An increasing number of radionuclides with therapeutic potential are now being produced, and can be stably attached to antigen-binding proteins, thanks to considerable advances in linker chemistry. Optimized radiolabeled antigen-binding constructs and multistep targeting systems are now being studied in clinical trials, and it appears that the goal of achieving adequate tumor radiation-absorbed dose may be at hand. Multimodality therapy is commonplace in cancer, and the rationale for combining radioimmunotherapy with other biologic therapy or chemotherapy is strong. These types of clinical trials are also being initiated. In this chapter, major antigen systems were highlighted after a brief discussion on radionuclides of therapeutic potential. There was also an overview of dosimetry methodology. Possible future directions for this promising therapy have also been discussed.

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