Imaging of a localized bacterial infection with endogenous thymidine kinase using radioisotope-labeled nucleosides

• Published in: International journal of medical microbiology Vol. 302; no. 2; pp. 101 - 107
• Main Authors: Jang, Su Jin, Lee, Yong Jin, Lim, Sangyong, Kim, Kwang Il, Lee, Kyo Chul, An, Gwang Il, Lee, Tae Sup, Cheon, Gi Jeong, Lim, Sang Moo, Kang, Joo Hyun
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.03.2012
• Subjects: Animal models; Animals; Arabinofuranosyluracil - analogs & derivatives; Bacteria; Bacterial infection; Bacterial Infections - diagnostic imaging; Bacterial Infections - metabolism; Data processing; Dideoxynucleosides; Focal Infection - diagnostic imaging; Focal Infection - metabolism; Gene Expression; Infection; Infectious Disease; Iodine Radioisotopes; Medical Education; Mice; Mice, Inbred BALB C; Molecular Imaging; Nuclear medicine; nucleosides; Positron emission tomography; Protein-tyrosine kinase; Radioactivity; Radioisotope; Radiopharmaceuticals; Salmonella typhimurium; Salmonella typhimurium - enzymology; Salmonella typhimurium - genetics; Single photon emission computed tomography; Thymidine kinase; Thymidine Kinase - analysis; Tomography, Emission-Computed, Single-Photon; Bacterial infection; Molecular imaging; Thymidine kinase; Radioisotope
• ISSN: 1438-4221; 1618-0607
• DOI: 10.1016/j.ijmm.2011.11.002

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 4 h 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.