Bacteria-targeted imaging using vancomycin-based positron emission tomography tracers can distinguish infection from sterile inflammation

Bacterial infections pose major challenges in medicine. To guide effective infection treatment, faster and more accurate diagnostic modalities are needed. Bacteria-targeted molecular imaging can meet these needs. The present study was aimed at the in vivo evaluation of two F-vancomycin-based PET tracers, for detection of deep-seated Gram-positive bacterial infections. These tracers were bench-marked against the current standard of care, [ F]FDG. The potential of [ F]BODIPY-FL-vancomycin and [ F]PQ-VE1-vancomycin ([4+2]photocycloadduct of 9,10-phenanthrenequinone-vancomycin and [ F]fluorinated vinyl ether) to distinguish bacterial infections from sterile inflammation was evaluated in a murine myositis model. Tracer specificity was assessed by infecting mice either with the Gram-positive bacterium Staphylococcus aureus (n = 12) or the Gram-negative bacterium Escherichia coli (n = 12). The contralateral leg was injected with Cytodex beads to induce sterile inflammation, or with phosphate-buffered saline for control. In parallel, mice were imaged with [ F]FDG (n = 12). Dynamic positron emission tomography (PET) measurements, biodistribution analyses, and immunohistopathology were performed to determine tracer distribution and bacterial burden. Both F-vancomycin-PET tracers accumulated at sites of infection, but not at sites of sterile inflammation, in contrast to [ F]FDG. The tracers exhibited distinct biodistribution profiles, with [ F]BODIPY-FL-vancomycin being cleared more rapidly. Both F-vancomycin-PET tracers displayed significant target to non-target ratios of 2.95 for [ F]BODIPY-FL-vancomycin and 1.48 for [ F]PQ-VE1-vancomycin. Vancomycin-based PET is a potentially attractive approach to distinguish Gram-positive bacterial infections from sterile inflammation.