Imaging bacterial infections with radiolabeled 1-(2′-deoxy-2′- fluoro-β-D-arabinofuranosyl)-5-iodouracil

Chetan Bettegowda, Catherine A. Foss, Ian Cheong, Yuchuan Wang, Luis Diaz, Nishant Agrawal, James Fox, James Dick, Long H. Dang, Shibin Zhou, Kenneth W. Kinzler, Bert Vogelstein, Martin G. Pomper

Research output: Contribution to journalArticle

Abstract

Bacterial infections provide diagnostic dilemmas that could be enlightened by modern imaging technologies. We have developed a simple method for imaging bacterial infections in mice that relies on the phosphorylation and trapping of the thymidine kinase (TK) substrate 1-(2′-deoxy-2′-fluoro-β-D- arabinofuranosyl)-5-[125I] iodouracil ([125I]FIAU) within bacteria. FIAU was found to inhibit the growth of WT Escherichia coli but not a TK- strain, indicating that WT E. coli could metabolize this compound. In silico analyses demonstrated that all pathogenic strains of bacteria whose genomes have been sequenced contain a TK gene highly homologous to the E. coli TK. Accordingly, we demonstrated that localized infections caused by representatives of five genera of bacteria could be readily imaged with [125I]FIAU. Such imaging provides a general method for the diagnosis of localized bacterial infections that could be translatable to the clinic.

Original languageEnglish (US)
Pages (from-to)1145-1150
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number4
DOIs
StatePublished - Jan 25 2005

Keywords

  • Nuclear medicine
  • Nucleoside analogs
  • Single-photon emission computed tomography
  • Thymidine kinase

ASJC Scopus subject areas

  • General

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