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Published on: January 11, 2020
Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography
Edward A Weinstein1, Alvaro A Ordonez2, Vincent P DeMarco3
1Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Abstract:
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-[(18)F]-fluorodeoxyglucose ((18)F-FDG) to produce 2-[(18)F]-fluorodeoxysorbitol ((18)F-FDS), a radioactive probe for Enterobacteriaceae, in 30 min. (18)F-FDS selectively accumulated in Enterobacteriaceae, but not in Gram-positive bacteria or healthy mammalian or cancer cells in vitro. In a murine myositis model, (18)F-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, (18)F-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 (18)F-FDS is a candidate imaging probe for translation to human clinical cases of known or suspected infections owing to Enterobacteriaceae.
Insights
A new radioactive probe, 2-[(18)F]-fluorodeoxysorbitol ((18)F-FDS), rapidly detects and localizes Enterobacteriaceae infections. This imaging tool monitors treatment efficacy and identifies drug-resistant bacteria in real-time.
Area of Science:
- Medical Imaging
- Infectious Diseases
- Radiochemistry
Background:
- Enterobacteriaceae are common causes of human infections, including multidrug-resistant and biothreat pathogens.
- Current diagnostic methods lack specificity and speed for timely infection detection and monitoring.
- Novel imaging tools are crucial for identifying Enterobacteriaceae infections and assessing antimicrobial efficacy.
Purpose of the Study:
- To develop and evaluate a novel radioactive probe for specific detection and localization of Enterobacteriaceae infections.
- To assess the probe's ability to differentiate bacterial infections from sterile inflammation.
- To determine the probe's utility in monitoring antimicrobial treatment response.
Main Methods:
- Synthesis of 2-[(18)F]-fluorodeoxysorbitol ((18)F-FDS) from 2-[(18)F]-fluorodeoxyglucose ((18)F-FDG) in 30 minutes.
- In vitro evaluation of (18)F-FDS accumulation in Enterobacteriaceae versus Gram-positive bacteria and mammalian cells.
- In vivo studies using positron emission tomography (PET) in murine models of myositis, co-infections, and chemotherapy-induced immunosuppression.
Main Results:
- (18)F-FDS selectively accumulated in Enterobacteriaceae, showing no uptake in Gram-positive bacteria or host cells in vitro.
- PET imaging with (18)F-FDS rapidly differentiated true Enterobacteriaceae infection from sterile inflammation in mice.
- The probe detected as few as 6.2 ± 0.2 log10 colony-forming units (CFU) of Escherichia coli and visualized infections in complex models.
- (18)F-FDS PET accurately monitored antimicrobial treatment efficacy, detecting therapeutic failures in real-time.
Conclusions:
- (18)F-FDS is a promising radioactive imaging probe for rapid and specific detection of Enterobacteriaceae infections.
- The probe enables real-time monitoring of antimicrobial therapy effectiveness.
- (18)F-FDS has potential for clinical translation in diagnosing and managing Enterobacteriaceae-related infections.
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