Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection

Ekaterina Dadachova, Antonio Nakouzi, Ruth A. Bryant, Arturo Casadevall

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

There is an urgent need for new antimicrobial therapies to combat drug resistance, new pathogens, and the relative inefficacy of current therapy in compromised hosts. Ionizing radiation can kill microorganisms quickly and efficiently, but this modality has not been exploited as a therapeutic antimicrobial strategy. We have developed methods to target ionizing radiation to a fungal cell by labeling a specific mAb with the therapeutic radioisotopes Rhenium-188 and Bismuth-213. Radiolabeled antibody killed cells of human pathogenic fungus Cryptococcus neoformans in vitro, thus converting an antibody with no inherent antifungal activity into a microbicidal molecule. Administration of radiolabeled antibody to mice with C. neoformans infection delivered 213Bi and 188Re to the sites of infection, reduced their organ fungal burden, and significantly prolonged their survival without apparent toxicity. This study establishes the principle that targeted radiation can be used for the therapy of an infectious disease, and suggests that it may have wide applicability as an antimicrobial strategy.

Original languageEnglish (US)
Pages (from-to)10942-10947
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number19
DOIs
StatePublished - Sep 16 2003
Externally publishedYes

Fingerprint

Mycoses
Ionizing Radiation
Antibodies
Cryptococcus neoformans
Rhenium
Therapeutics
Bismuth
Infection
Drug Resistance
Radioisotopes
Communicable Diseases
Fungi
Radiation
Survival

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection. / Dadachova, Ekaterina; Nakouzi, Antonio; Bryant, Ruth A.; Casadevall, Arturo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 19, 16.09.2003, p. 10942-10947.

Research output: Contribution to journalArticle

Dadachova, Ekaterina ; Nakouzi, Antonio ; Bryant, Ruth A. ; Casadevall, Arturo. / Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 19. pp. 10942-10947.
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