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Ahtinen H, Kulkova J, Lindholm L, et al. (68)Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections. EJNMMI Res. 2014;4:45doi: 10.1186/s13550-014-0045-3.
Ahtinen, H., Kulkova, J., Lindholm, L., Eerola, E., Hakanen, A. J., Moritz, N., Söderström, M., Saanijoki, T., Jalkanen, S., Roivainen, A., & Aro, H. T. (2014). (68)Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections. EJNMMI research, 445. https://doi.org/10.1186/s13550-014-0045-3
Ahtinen, Helena, et al. "(68)Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections." EJNMMI research vol. 4 (2014): 45. doi: https://doi.org/10.1186/s13550-014-0045-3
Ahtinen H, Kulkova J, Lindholm L, Eerola E, Hakanen AJ, Moritz N, Söderström M, Saanijoki T, Jalkanen S, Roivainen A, Aro HT. (68)Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections. EJNMMI Res. 2014 Aug 08;4:45. doi: 10.1186/s13550-014-0045-3. eCollection 2014. PMID: 25520903; PMCID: PMC4265888.
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EJNMMI Res. 2014 Aug 08;4:45. doi: 10.1186/s13550-014-0045-3. eCollection 2014.

(68)Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections.

EJNMMI research

Helena Ahtinen, Julia Kulkova, Laura Lindholm, Erkki Eerola, Antti J Hakanen, Niko Moritz, Mirva Söderström, Tiina Saanijoki, Sirpa Jalkanen, Anne Roivainen, Hannu T Aro

Affiliations

  1. Turku PET Centre, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
  2. Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
  3. Department of Medical Microbiology and Immunology, University of Turku, Turku FI-20521, Finland.
  4. Antimicrobial Resistance Unit, National Institute for Health and Welfare, Turku FI-20521, Finland.
  5. Turku Clinical Biomaterials Centre, Institute of Dentistry, University of Turku, Turku FI-20521, Finland.
  6. Department of Pathology, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
  7. Department of Medical Microbiology and Immunology, University of Turku, Turku FI-20521, Finland ; MediCity Research Laboratory, University of Turku, Turku FI-20521, Finland.
  8. Turku PET Centre, Turku University Hospital, University of Turku, Turku FI-20521, Finland ; Turku Center for Disease Modeling, University of Turku, Turku FI-20521, Finland.

PMID: 25520903 PMCID: PMC4265888 DOI: 10.1186/s13550-014-0045-3

Abstract

BACKGROUND: Staphylococcus epidermidis (S. epidermidis) has emerged as one of the leading pathogens of biomaterial-related infections. Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial molecule controlling extravasation of leukocytes. Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1. We hypothesized that (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated Siglec-9 motif containing peptide ((68)Ga-DOTA-Siglec-9) could detect inflammatory response due to S. epidermidis peri-implant infection by positron emission tomography (PET).

METHODS: Thirty Sprague-Dawley rats were randomized into three groups. A sterile catheter was implanted into the medullary canal of the left tibia. In groups 1 and 2, the implantation was followed by peri-implant injection of S. epidermidis or Staphylococcus aureus (S. aureus) with adjunct injections of aqueous sodium morrhuate. In group 3, sterile saline was injected instead of bacteria and no aqueous sodium morrhuate was used. At 2 weeks after operation, (68)Ga-DOTA-Siglec-9 PET coupled with computed tomography (CT) was performed with the measurement of the standardized uptake value (SUV). The presence of the implant-related infection was verified by microbiological analysis, imaging with fluorescence microscope, and histology. The in vivo PET results were verified by ex vivo measurements by gamma counter.

RESULTS: In group 3, the tibias with implanted sterile catheters showed an increased local uptake of (68)Ga-DOTA-Siglec-9 compared with the intact contralateral bones (SUVratio +29.5%). (68)Ga-DOTA-Siglec-9 PET detected inflammation induced by S. epidermidis and S. aureus catheter-related bone infections (SUVratio +58.1% and +41.7%, respectively). The tracer uptake was significantly higher in the S. epidermidis group than in group 3 without bacterial inoculation, but the difference between S. epidermidis and S. aureus groups was not statistically significant. The difference between the S. aureus group and group 3 was neither statistically significant.

CONCLUSION: PET/CT imaging with novel (68)Ga-DOTA-Siglec-9 tracer was able to detect inflammatory tissue response induced by catheter implantation and staphylococcal infections.

Keywords: 68Ga-DOTA-Siglec-9; Implant infection; Osteomyelitis; PET; S. aureus; S. epidermidis; VAP-1

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