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Purpose <p>Prosthetic joint- and fracture-related infections are major postoperative complications. Early, specific, and preferably non-invasive diagnostic tools, such as bacteria-targeting imaging agents, are essential for optimal treatment, since current approaches, including white blood cell scintigraphy and [¹⁸F]FDG-PET, are accurate, but may lack specificity. Vancomycin, an antibiotic targeting Gram-positive bacteria, has been successfully applied as a molecular scaffold for bacteria-specific tracer development. This study evaluated two novel vancomycin-based PET tracers, [¹⁸F]BODIPY-FL-vancomycin and [¹⁸F]VE1-PQ-vancomycin, along with the fluorescent tracer vancomycin-IRDye800CW, for diagnosing biofilm-associated orthopaedic implant infections.</p> Methods <p>We employed a preclinical in vivo model of orthopaedic implant infection, where C57BL/6 mice (<i>n</i> = 72) received stainless-steel Kirschner (K)-wire implants in the distal femur, which were inoculated with bioluminescent <i>Staphylococcus aureus</i> or <i>Escherichia coli</i> bacteria, or with PBS (sterile control). At days 13–14 post-implant infection, animals were injected with one of the vancomycin tracers or [¹⁸F]FDG (benchmark control) and underwent PET/CT or fluorescence imaging. Tracer accumulation at the infection site was quantified, followed by biodistribution analysis and bacterial load assessment.</p> Results <p>Both vancomycin-based PET tracers showed significantly higher uptake in <i>S. aureus</i>-infected legs compared to sterile controls. The differences in binding between <i>S. aureus</i> or <i>E. coli</i> were less distinct. In this model, [<sup>18</sup>F]FDG did not distinguish K-wire infection from sterile controls. Vancomycin-IRDye800CW accumulated specifically at <i>S. aureus</i> infection sites, but not at <i>E. coli</i> infection sites or sterile controls, indicating accurate bacteria-targeted imaging.</p> Conclusion <p>Vancomycin-based PET and optical tracers differentiated bacterial infection from the sterile K-wire controls in a murine model. Optical imaging distinguished Gram-positive from Gram-negative bacterial infection, whereas PET tracers did not. These preclinical findings support further investigation of vancomycin-based tracers for non-invasive imaging of prosthetic joint and fracture-related infections.</p>

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In vivo bacteria-targeted imaging with vancomycin-based positron emission tomography and optical tracers in an orthopaedic trauma implant infection model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Gerbren B. Spoelstra,
  • Lisanne M. Braams,
  • Frank F. A. IJpma,
  • Sjouke Piersma,
  • Carolien S. Braams,
  • Nicholas M. Bernthal,
  • Kevin P. Francis,
  • Andor W. J. M. Glaudemans,
  • Marleen van Oosten,
  • Ben L. Feringa,
  • Wiktor Szymanski,
  • Philip H. Elsinga,
  • Jan Maarten van Dijl

摘要

Purpose

Prosthetic joint- and fracture-related infections are major postoperative complications. Early, specific, and preferably non-invasive diagnostic tools, such as bacteria-targeting imaging agents, are essential for optimal treatment, since current approaches, including white blood cell scintigraphy and [¹⁸F]FDG-PET, are accurate, but may lack specificity. Vancomycin, an antibiotic targeting Gram-positive bacteria, has been successfully applied as a molecular scaffold for bacteria-specific tracer development. This study evaluated two novel vancomycin-based PET tracers, [¹⁸F]BODIPY-FL-vancomycin and [¹⁸F]VE1-PQ-vancomycin, along with the fluorescent tracer vancomycin-IRDye800CW, for diagnosing biofilm-associated orthopaedic implant infections.

Methods

We employed a preclinical in vivo model of orthopaedic implant infection, where C57BL/6 mice (n = 72) received stainless-steel Kirschner (K)-wire implants in the distal femur, which were inoculated with bioluminescent Staphylococcus aureus or Escherichia coli bacteria, or with PBS (sterile control). At days 13–14 post-implant infection, animals were injected with one of the vancomycin tracers or [¹⁸F]FDG (benchmark control) and underwent PET/CT or fluorescence imaging. Tracer accumulation at the infection site was quantified, followed by biodistribution analysis and bacterial load assessment.

Results

Both vancomycin-based PET tracers showed significantly higher uptake in S. aureus-infected legs compared to sterile controls. The differences in binding between S. aureus or E. coli were less distinct. In this model, [18F]FDG did not distinguish K-wire infection from sterile controls. Vancomycin-IRDye800CW accumulated specifically at S. aureus infection sites, but not at E. coli infection sites or sterile controls, indicating accurate bacteria-targeted imaging.

Conclusion

Vancomycin-based PET and optical tracers differentiated bacterial infection from the sterile K-wire controls in a murine model. Optical imaging distinguished Gram-positive from Gram-negative bacterial infection, whereas PET tracers did not. These preclinical findings support further investigation of vancomycin-based tracers for non-invasive imaging of prosthetic joint and fracture-related infections.