Pathogen-specific positron emission tomography for Enterobacterales bone infection

Gram-negative bone infections involving Enterobacterales group of bacteria pose a growing concern, especially for orthopaedic surgeries and diabetic ulcers. Current imaging methods either identify morphological changes by CT and MRI, or inflammation, using white blood cell scans or 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]-FDG) positron emission tomography (PET). While valuable, these are not specific, resulting in delayed diagnoses. PET/CT using 2-deoxy-2-[¹⁸F]fluoro-d-sorbitol ([¹⁸F]-FDS) is a novel method for detecting living Enterobacterales bacteria in vivo, via a conserved sorbitol-specific bacterial pathway. In this study, we aim to evaluate [¹⁸F]-FDS PET/CT for detection and monitoring of Enterobacterales bone infection in a mouse model.

We adapted a murine model of Gram-positive implant-associated spine infection to a Gram-negative infection model. We compared microbiological techniques to imaging with [¹⁸F]-FDG and [¹⁸F]-FDS. We determined the standardized uptake value (SUV) ratios for detection of bacterial infection and response to therapy, in 48 mice with surgical implants infected with either Escherichia coli or Staphylococcus aureus and compared them to controls with surgical implants but no infection.

Both bacteria induced substantial bone pathology with reduced bone density. [¹⁸F]-FDS PET could specifically detect implant-associated spinal infections due to E. coli with a mean SUV ratio of 2.2 (SD 1.3), which was substantially lower in S. aureus (0.7 (SD 0.2); p = 0.002) and uninfected mice (1.0 (SD 0.1)). In contrast, [¹⁸F]-FDG could not differentiate between the two bacterial infections or the control (p = 0.497). Finally, [¹⁸F]-FDS PET could determine antibiotic efficacy, and monitor infection over time.

We demonstrate that [¹⁸F]-FDS affords a highly accurate and clinically translatable detection of Enterobacterales bone infection. This novel modality offers a rapid and specific method to diagnose and monitor bone infections, inform medical decisions, reduce the need for surgery, and limit unnecessary antibiotic use. Similar approaches may be implemented to develop tracers for other bacteria.