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

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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 18F-vancomycin-based PET tracers, for detection of deep-seated Gram-positive bacterial infections. These tracers were bench-marked against the current standard of care, [18F]FDG. The potential of [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin ([4+2]photocycloadduct of 9,10-phenanthrenequinone-vancomycin and [18F]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 [18F]FDG (n = 12). Dynamic positron emission tomography (PET) measurements, biodistribution analyses, and immunohistopathology were performed to determine tracer distribution and bacterial burden. Both 18F-vancomycin-PET tracers accumulated at sites of infection, but not at sites of sterile inflammation, in contrast to [18F]FDG. The tracers exhibited distinct biodistribution profiles, with [18F]BODIPY-FL-vancomycin being cleared more rapidly. Both 18F-vancomycin-PET tracers displayed significant target to non-target ratios of 2.95 for [18F]BODIPY-FL-vancomycin and 1.48 for [18F]PQ-VE1-vancomycin. Vancomycin-based PET is a potentially attractive approach to distinguish Gram-positive bacterial infections from sterile inflammation.