A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses

Abstract

Aims Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (99mTc-UBI29-41-Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods. Methods 99mTc-UBI29-41-Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria. Results Bacteria could be effectively stained in vitro and on prostheses, irrespective of the presence of biofilm. Infected prostheses revealed bacterial presence on the transition zone between the head and neck, and in the screw hole. Qualitative 2D fluorescence images could be complemented with quantitative 3D fhSPECT scans. Despite thorough chlorhexidine treatments, 28% to 44% of the signal remained present in the locations of the infection that were identified using imaging, which included 500 to 2,000 viable bacteria. Conclusion The hybrid tracer 99mTc-UBI29-41-Cy5 allowed effective bacterial staining. Qualitative real-time fluorescence guidance could be effectively combined with nuclear imaging that enables quantitative monitoring of the effectiveness of cleaning strategies. Cite this article: Bone Joint Res 2023;12(1):72–79.

Insights into Peptidoglycan-Targeting Radiotracers for Imaging Bacterial Infections: Updates, Challenges, and Future Perspectives

“…This can be achieved through genetic manipulation or the use of targeted peptido­glycan inhibitors, such as antibiotics. ,, Also, for specific in vitro tests, the radioactive compounds should be evaluated using planktonic bacterial cultures, as in the clinical setting persistent or antimicrobial-resistant bacteria are often hidden in biofilms. This will improve the likeliness of translating results from pre-clinical evaluations further into the clinics …”

“…This will improve the likeliness of translating results from pre-clinical evaluations further into the clinics. 149 …”

Diagnostics in Late Periprosthetic Infections—Challenges and Solutions

“…Pathogen-specific hybrid tracers (e.g., 99mTc-UBI29-41-Cy5 for Staph. aureus infections) also represent a new diagnostic option and can also detect metabolically less active bacteria in the biofilm [33].…”