Radiofungicidal Effects of External Gamma Radiation and Antibody-Targeted Beta and Alpha Radiation

We evaluated the clonogenic survival, membrane permeability, metabolic activity (XTT reduction), and apoptosis (FLICA binding) of Cryptococcus neoformans cells subjected to gamma rays from an external source, and beta and alpha particles delivered to fungal cells by capsule-specific antibody. We found that gamma, beta, and alpha radiation affected cells through different pathways. Fungal cells such as Cryptococcus neoformans are extremely resistant to external gamma radiation (7), perhaps due to the extensive machinery that repairs UV-damaged DNA (11). In con-trast, C. neoformans is highly susceptible to beta and alpha radi-ation delivered by monoclonal antibodies (MAbs) specific for the polysaccharide capsule of C. neoformans (7, 8, 14), implying that damage by particulate radiation is different from gamma radia-tion damage. The susceptibility to antibody-delivered particulate radiation is the basis for the radioimmunotherapy (RIT) of cryp-tococcal infection (7, 8). RIT of C. neoformans-infected mice with alpha-emitter 213Bi- or beta-emitter 188Re-labeled C. neoforman