Current status and perspectives in alpha radioimmunotherapy

Systemic administration of radiolabeled antibody directed against tumor antigens in radioimmunotherapy (RIT) enables to specifically target the cancer cells and to destroy them. So far, this strategy has proven its efficiency in the treatment of some hematological cancers with antibodies labeled with beta emitting radionuclides. In the last 2 decades, availability of short half life alpha emitters prompted to consider their use in RIT. Contrary to beta particles, alpha particles have a short path length and display a high lineic energy transfer. Those physical characteristics open new fields of clinical applications complementary to beta-RIT. To date, alpha-RIT is still at a preclinical stage of development: the radiolabeling methods need to be optimized to ensure in vivo stability of the radiopharmaceuticals. Some radionuclides have complex decay schemes with daughters emitting further alpha particles whose toxicity needs to be investigated. The modalities of administration of radiolabeled antibodies in animal models require also to be improved for delivering higher doses to tumor targets. A comprehensive analysis of the specific events occurring at cell or tissue level in response to alpha irradiation would be of great interest in order to define the best therapeutic association for residual disease or consolidation treatments. This approach has been proven to be efficient in increasing antitumor response either by using high doses with organ protection (kidney, bone marrow) or by a synergistic effect between alpha-RIT and associated treatments, such as chemotherapy.