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Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography

2-[18F]-Fluorodeoxysorbitol, a synthetic PET probe, can be used to rapidly, sensitively, and specifically image Gram-negative bacterial infections in animals. Probing Bacterial infections with PET Imaging Often acquired in hospitals and notoriously resistant to many drugs, Enterobacteriaceae represent an infectious threat to human health. Pathogenic Enterobacteriaceae, including Escherichia coli and Klebsiella pneumoniae, readily metabolize the sugar sorbitol; thus, Weinstein and colleagues reasoned that a radiolabeled version of sorbitol could be used to image bacterial infections in vivo. The authors created 18F-fluorodeoxysorbitol (FDS) and administered it to mice for positron emission tomography (PET) imaging. The probe was able to distinguish E. coli infection from general inflammation as well as from infection with the Gram-positive bacteria Staphylococcus aureus. FDS was used to monitor antimicrobial efficacy in animals infected with drug-susceptible or drug-resistant E. coli. Such imaging would allow noninvasive monitoring of disease progression or regression, without repeated time-consuming cultures. Whole-body imaging of bacteria using PET and 18F-labeled probes—two common clinical tools—could provide clinicians with a sensitive and specific means of rapidly assessing infection and making treatment decisions. The Enterobacteriaceae are a family of rod-shaped Gram-negative bacteria that normally inhabit the gastrointestinal tract and are the most common cause of Gram-negative bacterial infections in humans. In addition to causing serious multidrug-resistant, hospital-acquired infections, a number of Enterobacteriaceae species are also recognized as biothreat pathogens. As a consequence, new tools are urgently needed to specifically identify and localize infections due to Enterobacteriaceae and to monitor antimicrobial efficacy. In this report, we used commercially available 2-[18F]-fluorodeoxyglucose (18F-FDG) to produce 2-[18F]-fluorodeoxysorbitol (18F-FDS), a radioactive probe for Enterobacteriaceae, in 30 min. 18F-FDS selectively accumulated in Enterobacteriaceae, but not in Gram-positive bacteria or healthy mammalian or cancer cells in vitro. In a murine myositis model, 18F-FDS positron emission tomography (PET) rapidly differentiated true infection from sterile inflammation with a limit of detection of 6.2 ± 0.2 log10 colony-forming units (CFU) for Escherichia coli. Our findings were extended to models of mixed Gram-positive and Gram-negative thigh co-infections, brain infection, Klebsiella pneumonia, and mice undergoing immunosuppressive chemotherapy. This technique rapidly and specifically localized infections due to Enterobacteriaceae, providing a three-dimensional holistic view within the animal. Last, 18F-FDS PET monitored the efficacy of antimicrobial treatment, demonstrating a PET signal proportionate to the bacterial burden. Therapeutic failures associated with multidrug-resistant, extended-spectrum β-lactamase (ESBL)–producing E. coli infections were detected in real time. Together, these data show that 18F-FDS is a candidate imaging probe for translation to human clinical cases of known or suspected infections owing to Enterobacteriaceae.