title: Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography.
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.
authors.affiliation: Center 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.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Weinstein
authors.affiliation: Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Ordonez
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Vincent P
authors.initials: VP
authors.lastname: DeMarco
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Murawski
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Supriya
authors.initials: S
authors.lastname: Pokkali
authors.affiliation: Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: MacDonald
authors.affiliation: Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Mariah
authors.initials: M
authors.lastname: Klunk
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.affiliation: Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.affiliation: Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. sjain5@jhmi.edu.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000000981:diagnostic imaging; D002460:Cell Line; D004756:Enterobacteriaceae Infections / Q000000981:diagnostic imaging* / Q000188:drug therapy; D004926:Escherichia coli / Q000472:pathogenicity; D005260:Female; D006801:Humans; D007121:Immunocompetence / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D007710:Klebsiella Infections / Q000000981:diagnostic imaging / Q000188:drug therapy; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009220:Myositis / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D011859:Radiography; D013012:Sorbitol / Q000031:analogs & derivatives*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000890:Anti-Infective Agents; D013012:Sorbitol