Radiolabelled Monoclonal Antibodies in the Treatment of Metastatic Cancer

Most cancer patients die from advanced, metastatic disease. Because surgery and external irradiation are the best prospects for treating localized disease (although both have also been applied to limited treatment of metastatic disease), systemic chemotherapy—and more recently, immunotherapy—are the mainstays of treating cancer that has become disseminated. Systemic chemotherapy is accompanied by dose-limiting toxicities to various organ systems, particularly the rapid proliferating cells of the oral and intestinal mucosa, bone marrow, and hair follicles, and agents that target antibodies are usually less potent, cause infusion or flu-like reactions, and are most effective in combination with cytotoxic drugs 1,2. Another class of agents that combines the foregoing properties has emerged in the form of radiolabelled antibodies, which harness the ability of antibodies against cancer antigens to localize to cancer cells, and the cytotoxicity of the radiation carried by the antibodies. In 1978, I named this method, then in its infancy, “radioimmunotherapy” 3. The last quarter-century has witnessed development in all aspects of this therapy, such as choice of antibody and antibody form, selection of therapeutic radionuclide, conjugation chemistry, and tumour target and clinical setting. These aspects have been reviewed elsewhere 4–7, and so they will not be the principal focus of this article. Instead, I will summarize the status, including problems and prospects, for the application of radioimmunotherapy in the treatment of meta-static cancer.