Specific imaging of bacterial infection: a translational approach using positron emission tomography and...

Direct visualization of the presence and biological activity of bacterial pathogens in infectious foci may be of considerable value for individualized infection medicine. We hypothesized that a positron-emitting maltodextrin radiotracer [⁶⁸Ga]Gallium-DOTA-maltohexaose ([⁶⁸Ga]Ga-DMALTO) could sensitively and translationally distinguish between bacterial infection and aseptic inflammation in a clinical application.

A new radiosynthesis of [⁶⁸Ga]Ga-DMALTO was established and transferred to an automated good manufacturing practice-compatible automated setting. [⁶⁸Ga]Ga-DMALTO was analyzed in vitro in bacterial strains and macrophages followed by in vivo positron emission tomography (PET) in healthy/infected/inflamed mouse models. Finally, it was examined in an early clinical application in patients with left-ventricular assist device infection, requiring precise localization of infection foci.

A robust, high-yield radiosynthesis of [⁶⁸Ga]Ga-DMALTO was established and in vitro-assays confirmed specific uptake in bacteria with no uptake in macrophages. In mouse models, [⁶⁸Ga]Ga-DMALTO was rapidly cleared via renal excretion with minimal background in healthy tissue. In the presence of Gram-negative (Escherichia coli) or Gram-positive (Bacillus subtilis) bacterial infection the [⁶⁸Ga]Ga-DMALTO signal was specifically located in infected hindlimbs, which was not observed in sterile inflammation models. By contrast, the standard clinical tracer 2-[¹⁸F]Fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) did not distinguish between infection and aseptic inflammation. The clinical application of [⁶⁸Ga]Ga-DMALTO in patients with left-ventricular assist device infection confirmed renal clearance and low background, and demonstrated specific accumulation in proven infectious foci along the driveline path. In comparison with [¹⁸F]FDG, focal [⁶⁸Ga]Ga-DMALTO uptake was reproducible but less intense, supporting a complementary role for the in vivo imaging of viable bacterial burden and host inflammatory responses.

The hypothesis-generating results of our work lay the foundation for future studies determining the specific benefit of bacteria-targeted in vivo imaging for clinical decision making and anti-infectious therapy guidance.