Localized bacterial infection imaging using bacterial thymidine kinase activity

Objectives Conventional diagnostic methods for infections are difficult to distinguish localized bacterial infections from sites of sterile inflammation. For this reason, the importance of developing methods to image bacterial infections is widely recognized. In this study to acquire bacterial infection imaging with radiolabeled nucleosides, in vitro bacterial thymidine kinase activities of Salmonella typhimurium were measured and localized infections model was imaged with [18F]FLT or [125I]FIAU.

Methods Two different kinds of attenuated Salmonella strains, VNP20009 (msbB-, purI-) and BH129 (ptsI-), were genetically engineered to express lux genes, and the resulting strains were named as VNP20009-Lux and BH129-Lux. We determined bacterial uptake with 370 KBq of [18F]FLT or 74 KBq of [125I]FIAU according to time intervals at 1×10^6 colony forming unit (cfu). Localized infections were generated by injecting 1×10^8 or 1×10^9 cfu/mouse of the two bacterial strains into thigh muscle of BALB/c mouse. Four hours later, bacterial localization was determined with IVIS-200 (Xenogen). Two hours later, 11.1 MBq of [125I]FIAU or 7.4 MBq of [18F]FLT were intravenously injected by mice and images were taken using INVEON (Siemens).

Results The accumulated radioactivity showed a linearly increased pattern with increasing incubation time or bacterial numbers. [18F]FLT and [125I]FIAU uptake ratio of BH129-Lux to VNP20009-Lux at 1×10^5 cfu for 120 min were 5.85 and 1.89, respectively. The image clearly demonstrated high uptake of [125I]FIAU and [18F]FLT in bacterial infection site. FLT uptake in the infection site was 7.286±2.405, while the uptake in non-infected site was 0.519±0.561.

Conclusions In conclusion, we demonstrated that bacterial tk activity was confirmed by cellular uptake and nuclear medicine imaging with [125I]FIAU or [18F]FLT. Therefore, the localized bacterial infection in mice could be monitored using a radiolabeled bacterial tk substrate with nuclear medicine modality