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

Igor Shuryak, Ruth A. Bryan, Jack Broitman, Stephen A. Marino, Alfred Morgenstern, Christos Apostolidis, Ekaterina Dadachova

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 <sup>213</sup>Bi-labeled monoclonal antibodies), and sparsely-ionizing <sup>137</sup>Cs γ-rays, on Cryptococus neoformans. Results: The best-fit linear-quadratic parameters for clonogenic survival were the following: α=0.24×10<sup>-2</sup>Gy<sup>-1</sup> for γ-rays and 1.07×10<sup>-2</sup>Gy<sup>-1</sup> for external-beam α-particles, and β=1.44×10<sup>-5</sup>Gy<sup>-2</sup> 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.

Original languageEnglish (US)
Pages (from-to)515-523
Number of pages9
JournalNuclear Medicine and Biology
Volume42
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Cryptococcus neoformans
Radiation Effects
Ionizing Radiation
Eukaryota
Antibodies
Fungi
Mycoses
Cell Nucleus
Cell Death
Monoclonal Antibodies
Radiation
Survival
Research

Keywords

  • Alpha particles
  • Cryptococcus neoformans
  • Radiation
  • Radiolabeled antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Shuryak, I., Bryan, R. A., Broitman, J., Marino, S. A., Morgenstern, A., Apostolidis, C., & Dadachova, E. (2015). Effects of radiation type and delivery mode on a radioresistant eukaryote Cryptococcus neoformans. Nuclear Medicine and Biology, 42(6), 515-523. https://doi.org/10.1016/j.nucmedbio.2015.02.006

Effects of radiation type and delivery mode on a radioresistant eukaryote Cryptococcus neoformans. / Shuryak, Igor; Bryan, Ruth A.; Broitman, Jack; Marino, Stephen A.; Morgenstern, Alfred; Apostolidis, Christos; Dadachova, Ekaterina.

In: Nuclear Medicine and Biology, Vol. 42, No. 6, 01.06.2015, p. 515-523.

Research output: Contribution to journalArticle

Shuryak, I, Bryan, RA, Broitman, J, Marino, SA, Morgenstern, A, Apostolidis, C & Dadachova, E 2015, 'Effects of radiation type and delivery mode on a radioresistant eukaryote Cryptococcus neoformans', Nuclear Medicine and Biology, vol. 42, no. 6, pp. 515-523. https://doi.org/10.1016/j.nucmedbio.2015.02.006
Shuryak, Igor ; Bryan, Ruth A. ; Broitman, Jack ; Marino, Stephen A. ; Morgenstern, Alfred ; Apostolidis, Christos ; Dadachova, Ekaterina. / Effects of radiation type and delivery mode on a radioresistant eukaryote Cryptococcus neoformans. In: Nuclear Medicine and Biology. 2015 ; Vol. 42, No. 6. pp. 515-523.
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