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

Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1145-50. doi: 10.1073/pnas.0408861102. Epub 2005 Jan 14.

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-beta-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arabinofuranosyluracil / analogs & derivatives*
  • Arabinofuranosyluracil / metabolism
  • Cell Line
  • Escherichia coli / enzymology
  • Escherichia coli Infections / diagnostic imaging*
  • Humans
  • Iodine Radioisotopes*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Radionuclide Imaging
  • Thymidine Kinase / genetics*

Substances

  • Iodine Radioisotopes
  • Arabinofuranosyluracil
  • fialuridine
  • Thymidine Kinase