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

• Published in: Science translational medicine Vol. 6; no. 259; p. 259ra146
• Main Authors: Weinstein, Edward A, Ordonez, Alvaro A, DeMarco, Vincent P, Murawski, Allison M, Pokkali, Supriya, MacDonald, Elizabeth M, Klunk, Mariah, Mease, Ronnie C, Pomper, Martin G, Jain, Sanjay K
• Format: Journal Article
• Language: English
• Published: United States 22-10-2014
• Subjects: Animals; Anti-Infective Agents - pharmacology; Anti-Infective Agents - therapeutic use; Brain Neoplasms - diagnostic imaging; Cell Line; Enterobacteriaceae Infections - diagnostic imaging; Enterobacteriaceae Infections - drug therapy; Escherichia coli - pathogenicity; Female; Humans; Immunocompetence - drug effects; Inflammation - pathology; Klebsiella Infections - diagnostic imaging; Klebsiella Infections - drug therapy; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - physiology; Mice; Microbial Sensitivity Tests; Myositis - diagnostic imaging; Positron-Emission Tomography; Radiography; Sorbitol - analogs & derivatives; Xenograft Model Antitumor Assays
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.3009815

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.