Radioimmunotherapy of human tumours

Key Points Antibodies with practical healthcare applications are being introduced into modern medicine at a rapid pace by academic laboratories and industry. Therapeutic applications of these biologics are becoming increasingly important for cancer, either by promoting the body's own defence against the tumour or as a carrier for immunotoxins, drugs or radiation. Radioimmunotherapy, which is the subject of this Review, exploits the immune protein as a carrier for radioactive isotopes, tracers or targeted therapeutics. The radioantibody is introduced into the blood or a body cavity such as the peritoneum, pleura or intrathecal space, and is carried to its natural target or antigen-binding site on the tumour cell by blood flow, diffusion or the bulk flow of fluid. Cancer cells naturally produce cancer-associated biological molecules, which are adaptive features of malignant change that are suitable as antigenic binding sites owing to their relatively high abundance in cancer cells in comparison to normal tissues. These cancer-associated antigens may be located in the membrane, cytoplasm or organelles, including the nucleus. Typical concentrations of target antigens are in the nanomolar to low micromolar range. Cancer-selective antibodies and related immunoproteins are particularly well suited for conjugation with radioisotopes, for the purpose of detection or targeted radiotherapy. As a rule of thumb, the concentration of antibody at the binding site should approximate but not exceed the concentration of antigen (that is, the nanomolar range), and this amount of carrier is enormous relative to the required concentrations of attached radioisotopes for detection or therapy. This is because radioisotopes are among the most energetic moieties known, and this energy can be used for imaging or radiotherapy when attached to antibodies, in the femto-molar to pico-molar range. The modern manufacture of tumour-selective antibodies bearing tumour-killing radioactive cargo has effectively harnessed the power of the atom to safely destroy cancer cells. This Review presents fundamental concepts of chemistry, physics and biology that are essential for the effective radioimmunotherapy of human cancer. The eradication of cancer remains a vexing problem despite recent advances in our understanding of the molecular basis of neoplasia. One therapeutic approach that has demonstrated potential involves the selective targeting of radionuclides to cancer-associated cell surface ant