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

Abstract

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.

Sex Differences in Lung Imaging and SARS-CoV-2 Antibody Responses in a COVID-19 Golden Syrian Hamster Model

“…Live animals were imaged inside in-house-developed, sealed biocontainment devices compliant with BSL-3, as previously reported ( 56 ). Seven days postinfection, SARS-CoV-2-infected male ( n = 12), female ( n = 12), placebo-treated male ( n = 13), and E2-treated male ( n = 13) hamsters underwent chest CT using the nanoScan positron emission tomography (PET)/CT (Mediso USA, MA, USA) small animal imager.…”

[18F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound

“…Further experiments are however needed to validate the use of [ 18 F]FDS to quantitatively monitor the permeability of the blood-tumor barrier. Similarly, we advocate that the high sensitivity of [ 18 F]FDS to BBB integrity may be considered for correct estimation of bacterial burden in brain lesions using [ 18 F]FDS PET [37].…”

“…Efforts are moreover being made to develop kit formulation for radiosynthesis of [ 18 F]FDS to simplify the production of this radiopharmaceutical [45]. Radiosynthesis of [ 18 F]FDS for animal or clinical use can therefore be achieved in most molecular imaging departments, including those not equipped with radiochemistry facilities [37]. From a clinical perspective, the radiation dosimetry of this radiopharmaceutical was shown suitable for human use, although radiation exposure can be a limitation for the repeated use of [ 18 F]FDS PET in humans [30].…”

Pathophysiology and Molecular Imaging of Diabetic Foot Infections

“…A more recent study of 18 F-FDS demonstrated the sorbitol-specific pathway by observing uptake in clinically relevant strains of Enterobacterales. Following the in vitro study and a previous in vivo study in murine models, they acquired 18 F-FDS PET/CT images in humans, demonstrating the safety and ability of 18 F-FDS to differentiate infection from sterile inflammation [141]. In addition, it was used to monitor antibiotic treatment [140].…”