title: (68)Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Ahtinen
authors.affiliation: Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
authors.forename: Julia
authors.initials: J
authors.lastname: Kulkova
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku FI-20521, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Lindholm
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku FI-20521, Finland.
authors.forename: Erkki
authors.initials: E
authors.lastname: Eerola
authors.affiliation: Antimicrobial Resistance Unit, National Institute for Health and Welfare, Turku FI-20521, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Hakanen
authors.affiliation: Turku Clinical Biomaterials Centre, Institute of Dentistry, University of Turku, Turku FI-20521, Finland.
authors.forename: Niko
authors.initials: N
authors.lastname: Moritz
authors.affiliation: Department of Pathology, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
authors.forename: Mirva
authors.initials: M
authors.lastname: Söderström
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Saanijoki
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku FI-20521, Finland ; MediCity Research Laboratory, University of Turku, Turku FI-20521, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.affiliation: Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
authors.forename: Hannu T
authors.initials: HT
authors.lastname: Aro
keywords: 68Ga-DOTA-Siglec-9; Implant infection; Osteomyelitis; PET; S. aureus; S. epidermidis; VAP-1