title: Imaging of a localized bacterial infection with endogenous thymidine kinase using radioisotope-labeled nucleosides.
abstract: The importance of noninvasive imaging methods to bacterial infections is widely recognized. To obtain bacterial infection imaging with radioisotope-labeled nucleosides, bacterial thymidine kinase (tk) activities of Salmonella typhimurium with [(125)I]5-iodo-1-(2'-fluoro-2'-deoxy-β-d-arabinofuranosyl)uracil ([(125)I]FIAU) or 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) were measured. The infection model in BALB/c mice was imaged with [(125)I]FIAU or [(18)F]FLT using small-animal Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET), respectively. The accumulated radioactivity of [(125)I]FIAU or [(18)F]FLT in the two strains showed a linearly increased pattern with increasing incubation time or bacterial numbers. The image clearly demonstrated a high uptake of [(125)I]FIAU and [(18)F]FLT in the bacterial infection site. [(18)F]FLT uptake in the infection site of was 7.286±2.405, whereas that in the uninfected site was 0.519±0.561. The relative activity ratio of the infected region in relation to the uninfected region was 2.98 at 4h after an injection with [(125)I]FIAU determined by biodistribution data. In conclusion, the bacterial tk activity was confirmed by the cellular uptake and imaging with [(125)I]FIAU or [(18)F]FLT. Therefore, a localized bacterial infection in living mice can be monitored using radioisotope-labeled nucleosides with a nuclear medicine imaging modality.
authors.affiliation: Molecular Imaging Research Center, Seoul, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Jang
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sangyong
authors.initials: S
authors.lastname: Lim
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: An
authors.forename: Tae Sup
authors.initials: TS
authors.lastname: Lee
authors.forename: Gi Jeong
authors.initials: GJ
authors.lastname: Cheon
authors.forename: Sang Moo
authors.initials: SM
authors.lastname: Lim
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives*; D001424:Bacterial Infections / Q000000981:diagnostic imaging* / Q000378:metabolism; D015224:Dideoxynucleosides; D005490:Focal Infection / Q000000981:diagnostic imaging* / Q000378:metabolism; D015870:Gene Expression; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000032:analysis*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015224:Dideoxynucleosides; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; C043457:fialuridine; D013937:Thymidine Kinase; C002854:alovudine