Background: Staphylococcus epidermidis (S. epidermidis) has emerged as one of the leading pathogens of\nbiomaterial-related infections. Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial molecule\ncontrolling extravasation of leukocytes. Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand\nof VAP-1. We hypothesized that 68Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated\nSiglec-9 motif containing peptide (68Ga-DOTA-Siglec-9) could detect inflammatory response due to S. epidermidis\nperi-implant infection by positron emission tomography (PET).\nMethods: Thirty Sprague-Dawley rats were randomized into three groups. A sterile catheter was implanted into\nthe medullary canal of the left tibia. In groups 1 and 2, the implantation was followed by peri-implant injection of\nS. epidermidis or Staphylococcus aureus (S. aureus) with adjunct injections of aqueous sodium morrhuate. In group 3,\nsterile saline was injected instead of bacteria and no aqueous sodium morrhuate was used. At 2 weeks after operation,\n68Ga-DOTA-Siglec-9 PET coupled with computed tomography (CT) was performed with the measurement of the\nstandardized uptake value (SUV). The presence of the implant-related infection was verified by microbiological\nanalysis, imaging with fluorescence microscope, and histology. The in vivo PET results were verified by ex vivo\nmeasurements by gamma counter.\nResults: In group 3, the tibias with implanted sterile catheters showed an increased local uptake of 68Ga-DOTA-Siglec-9\ncompared with the intact contralateral bones (SUVratio +29.5%). 68Ga-DOTA-Siglec-9 PET detected inflammation induced\nby S. epidermidis and S. aureus catheter-related bone infections (SUVratio +58.1% and +41.7%, respectively). The tracer\nuptake was significantly higher in the S. epidermidis group than in group 3 without bacterial inoculation, but the\ndifference between S. epidermidis and S. aureus groups was not statistically significant. The difference between\nthe S. aureus group and group 3 was neither statistically significant.\nConclusion: PET/CT imaging with novel 68Ga-DOTA-Siglec-9 tracer was able to detect inflammatory tissue\nresponse induced by catheter implantation and staphylococcal infections.
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