Imaging bacterial infections with radiolabeled 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil.
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.
Bettegowda
Chetan
C
Howard Hughes Medical Institute and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Foss
Catherine A
CA
Cheong
Ian
I
Wang
Yuchuan
Y
Diaz
Luis
L
Agrawal
Nishant
N
Fox
James
J
Dick
James
J
Dang
Long H
LH
Zhou
Shibin
S
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Pomper
Martin G
MG
D000595:Amino Acid Sequence; D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000378:metabolism; D002460:Cell Line; D004926:Escherichia coli / Q000201:enzymology; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging*; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011877:Radionuclide Imaging; D013937:Thymidine Kinase / Q000235:genetics*
D007457:Iodine Radioisotopes; D001086:Arabinofuranosyluracil; C043457:fialuridine; D013937:Thymidine Kinase