Micro-PET imaging of [18F]fluoroacetate combined with [18F]FDG to differentiate chronic Mycobacterium tuberculosis infection from an acute bacterial infection in a mouse model

BACKGROUND: Mycobacterium tuberculosis (TB) infection is one of the deadliest infectious diseases worldwide and is responsible for 1.7 million deaths per year. The increase in multidrug-resistant TB poses formidable challenges to the global control of tuberculosis. TB infection could easily yield false-positive results in fluorine-18-fluorodeoxyglucose ([F]FDG) PET imaging for cancer detection because of its high [F]FDG uptake. We describe the combined [F]FDG PET with fluorine-18-fluoroacetate ([F]FAC), a promising analog of carbon-11-acetate, for targeting glycolysis and de novo lipogenesis, respectively, to determine the metabolic differences between chronic TB infection and acute infection. MATERIALS AND METHODS: Six-month-old BALB/c mice were inoculated with Mycobacterium bovis to induce chronic TB infection, and Escherichia coli as well as Staphylococcus aureus to induce acute infection for an in-vivo imaging study. Eighteen days after inoculation for chronic TB infection and 5 days for acute infection, both [F]FDG and [F]FAC micro-PET were performed on the infected mice. Analysis of variance and the Tukey honest ad-hoc test were carried out to determine differences among treatment with different bacterial infections. RESULTS: TB infection showed much lower [F] FAC accumulation than acute infection. However, both TB infection and acute infection exhibited high [F]FAC accumulation. CONCLUSION: The marked metabolic differences in de novo lipogenesis and glycolysis in [F]FDG and [F]FAC uptakes in micro-PET imaging, respectively, help to differentiate chronic TB infection from acute infection.