Specific imaging of bacterial infection: a translational approach using positron emission tomography and gallium-68-labeled maltohexaose.

Abstract

RATIONALE: 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 [Ga]Gallium-DOTA-maltohexaose ([Ga]Ga-DMALTO) could sensitively and translationally distinguish between bacterial infection and aseptic inflammation in a clinical application. METHODS: A new radiosynthesis of [Ga]Ga-DMALTO was established and transferred to an automated good manufacturing practice-compatible automated setting. [Ga]Ga-DMALTO was analyzedin bacterial strains and macrophages followed bypositron 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. RESULTS: A robust, high-yield radiosynthesis of [Ga]Ga-DMALTO was established and-assays confirmed specific uptake in bacteria with no uptake in macrophages. In mouse models, [Ga]Ga-DMALTO was rapidly cleared via renal excretion with minimal background in healthy tissue. In the presence of Gram-negative () or Gram-positive () bacterial infection the [Ga]Ga-DMALTO signal was specifically located in infected hindlimbs, which was not observed in sterile inflammation models. By contrast, the standard clinical tracer 2-[F]Fluoro-2-deoxy-D-glucose ([F]FDG) did not distinguish between infection and aseptic inflammation. The clinical application of [Ga]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 [F]FDG, focal [Ga]Ga-DMALTO uptake was reproducible but less intense, supporting a complementary role for theimaging of viable bacterial burden and host inflammatory responses. CONCLUSIONS: The hypothesis-generating results of our work lay the foundation for future studies determining the specific benefit of bacteria-targetedimaging for clinical decision making and anti-infectious therapy guidance.