Effects of radiation type and delivery mode on a radioresistant eukaryote Cryptococcus neoformans

Introduction: Most research on radioresistant fungi, particularly on human pathogens such as Cryptococcus neoformans, involves sparsely-ionizing radiation. Consequently, fungal responses to densely-ionizing radiation, which can be harnessed to treat life-threatening fungal infections, remain incompletely understood. Methods: We addressed this issue by quantifying and comparing the effects of densely-ionizing α-particles (delivered either by external beam or by ²¹³Bi-labeled monoclonal antibodies), and sparsely-ionizing ¹³⁷Cs γ-rays, on Cryptococus neoformans. Results: The best-fit linear-quadratic parameters for clonogenic survival were the following: α=0.24×10^-2Gy^-1 for γ-rays and 1.07×10^-2Gy^-1 for external-beam α-particles, and β=1.44×10^-5Gy^-2 for both radiation types. Fungal cell killing by radiolabeled antibodies was consistent with predictions based on the α-particle dose to the cell nucleus and the linear-quadratic parameters for external-beam α-particles. The estimated RBE (for α-particles vs. γ-rays) at low doses was 4.47 for the initial portion of the α-particle track, and 7.66 for the Bragg peak. Non-radiological antibody effects accounted for up to 23% of cell death. Conclusions: These results quantify the degree of C. neoformans resistance to densely-ionizing radiations, and show how this resistance can be overcome with fungus-specific radiolabeled antibodies.