Radioimmunotherapy of infection with Bi-labeled antibodies

Bismuth-213 ((213)Bi) (physical half-life 46 min) is a beta-emitter (97%) and an alpha-emitter (3%) which decays to short lived alpha-emitter Polonium-213 and could therefore be used as an in vivo generator of alpha particles with the energy of around 8 MeV. (213)Bi has been successfully used during the last decade in both clinical and pre-clinical work for radioimmunotherapy (RIT) of cancer with (213)Bi-labeled monoclonal antibodies (mAbs). RIT has been proposed as a novel techonology for treatment of infectious diseases. (213)Bi-labeled mAbs have been successfully used for treatment of experimental fungal, bacterial and viral infections with transient or none hematologic toxicity. The mechanisms of RIT of infection with (213)Bi-labeled mAbs include "direct" killing of cells and induction of apoptosis. In vivo RIT results in decrease of inflammation in infected organs. Among the delivery vehicles for RIT of infection whole IgG1 mAbs seem to be the most suitable in terms of the highest uptake in the target organs and the lowest - in normal tissues. RIT with alpha-emitter (213)Bi involves the application of established technology developed for the treatment of malignancies to infectious diseases. The development of RIT for infectious diseases is potentially easier than its application to tumor therapy given antigenic and tissue perfusion differences between sites of microbial infection and tumor infiltration. Nevertheless, considerable pre-clinical and clinical development work is likely to be required to learn how to use RIT for infection optimally.