Imaging Enterobacterales infections in patients using pathogen-specific positron emission tomography

Abstract

18F-FDS PET/CT can detect and localize infections due to Enterobacterales in patients and noninvasively monitor response to antibiotic treatment. Pathogen-specific PET Enterobacterales infections can affect diverse locations within the body, and multidrug-resistant strains are difficult to diagnose and treat. Ordonez et al. used 18F-FDS as a bacteria-specific imaging agent to detect and monitor infections in patients. Positron emission tomography/computerized tomography (PET/CT) imaging showed selective uptake of the tracer in Enterobacterales infections as opposed to other types of inflammation or cancer. Signal was reduced in sites of drug-susceptible infections in patients after treatment with antibiotics. The authors also showed that the imaging agent could differentiate bacterial infection from SARS-CoV-2 in a hamster model, supporting the use of 18F-FDS for bacteria-specific imaging. Enterobacterales represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. We previously demonstrated that positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-sorbitol (18F-FDS) can selectively detect Enterobacterales infections in murine models. Here, we demonstrate that uptake of 18F-FDS by bacteria occurs via a metabolically conserved sorbitol-specific pathway with rapid in vitro 18F-FDS uptake noted in clinical strains, including MDR isolates. Whole-body 18F-FDS PET/computerized tomography (CT) in 26 prospectively enrolled patients with either microbiologically confirmed Enterobacterales infection or other pathologies demonstrated that 18F-FDS PET/CT was safe, could rapidly detect and localize Enterobacterales infections due to drug-susceptible or MDR strains, and differentiated them from sterile inflammation or cancerous lesions. Repeat imaging in the same patients monitored antibiotic efficacy with decreases in PET signal correlating with clinical improvement. To facilitate the use of 18F-FDS, we developed a self-contained, solid-phase cartridge to rapidly (<10 min) formulate ready-to-use 18F-FDS from commercially available 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) at room temperature. In a hamster model, 18F-FDS PET/CT also differentiated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from secondary Klebsiella pneumoniae pneumonia—a leading cause of complications in hospitalized patients with COVID-19. These data support 18F-FDS as an innovative and readily available, pathogen-specific PET technology with clinical applications.