title: Effects of radiation type and delivery mode on a radioresistant eukaryote Cryptococcus neoformans.
abstract: BACKGROUND
  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 (213)Bi-labeled monoclonal antibodies), and sparsely-ionizing (137)Cs γ-rays, on Cryptococcus neoformans.
  
  
  RESULTS
  The best-fit linear-quadratic parameters for clonogenic survival were the following: α = 0.24 × 10(-2) Gy(-1) for γ-rays and 1.07 × 10(-2) Gy(-1) for external-beam α-particles, and β = 1.44 × 10(-5) Gy(-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.
authors: Center for Radiological Research, Columbia University Medical Center, New York, New York.
authors: Igor
authors: I
authors: Shuryak
authors: Department of Radiology, Albert Einstein College of Medicine, Bronx, New York.
authors: Ruth A
authors: RA
authors: Bryan
authors: Department of Radiology, Albert Einstein College of Medicine, Bronx, New York.
authors: Jack
authors: J
authors: Broitman
authors: Radiological Research Accelerator Facility, Nevis Laboratories, Irvington, New York.
authors: Stephen A
authors: SA
authors: Marino
authors: European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany.
authors: Alfred
authors: A
authors: Morgenstern
authors: European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany.
authors: Christos
authors: C
authors: Apostolidis
authors: Department of Radiology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York. Electronic address: ekaterina.dadachova@einstein.yu.edu.
authors: Ekaterina
authors: E
authors: Dadachova
mesh_terms: D000512:Alpha Particles; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001729:Bismuth / Q000494:pharmacology; D016923:Cell Death / Q000528:radiation effects*; D002467:Cell Nucleus / Q000528:radiation effects*; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D011134:Polysaccharides / Q000276:immunology; D011836:Radiation Tolerance
chemical_list: D000911:Antibodies, Monoclonal; D011134:Polysaccharides; D001729:Bismuth
keywords: Alpha particles; Cryptococcus neoformans; Radiation; Radiolabeled antibodies