Targeted Radioimmunotherapy and Theranostics with Alpha Emitters

Radiolabeled antibodies allow for selective targeting of the cancer cells within a tumor. Both beta-and alpha-emitting radioisotopes can be linked to the antibodies for delivery of radiation to the cells. The choice of the radionuclide would depend on the biological characteristics of the antibody including its biodistribution and biological half-life. Alpha-emitting isotopes deliver high energy to target sites within short range and therefore less radiation to adjacent normal tissues. Whole antibodies have long biological clearance times that may be limiting due to radiation levels to blood and marrow. Novel strategies, such as development of smaller antibody fragments such as minibodies and diabodies, which have faster biological clearance, engineered bispecific antibodies, and multistep targeting that uses pre-targeting and bioorthogonal click chemistry methods, appear promising. Several novel targets are being investigated in early-phase studies. This review provides a brief summary and current status of radioimmunotargeted agents in oncology.