Radioimmunotherapy of infections using alpha- and beta-emitting radionuclides

NUCL 82

Ekaterina Dadachova1, Ruth Bryan2, Antonio Nakouzi3, Annie Frenkel2, Joshua D. Nosanchuk3, Andrew D. Schweitzer2, and Arturo Casadevall3. (1) Nuclear Medicine, Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461, (2) Albert Einstein College of Medicine, NY, (3) Microbiology and Immunology, Albert Einstein College of Medicine, NY
Fungal infections are notoriously difficult to treat in immunosuppressed patients and novel therapeutic modalities are urgently needed to eradicate infection in the setting of severe immune dysfunction. We have investigated the potential of radioimmunotherapy of C. neoformans and H. capsulatum fungal infections with organism-specific monoclonal antibodies (mAb) 18B7 and 9C7, respectively, radiolabeled with alpha-emitter 213-Bismuth and beta-emitter 188-Rhenium. Both C. neoformans and H. capsulatum proved to be extremely radioresistant to external gamma-radiation with significant killing of the cells observed only above 70,000 rad. On the contrary, two-log reduction in survival of fungal cells was achieved in vitro with 213-Bi- and 188-Re-labeled mAbís 18B7 and 9C7. This study demonstrates that RIT with organism-specific antibody can be an effective weapon against opportunistic fungal infection and suggests the potential usefulness of this modality against other infectious diseases.