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

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

doi:10.1186/s13550-014-0045-3

Abstract

BackgroundStaphylococcus 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 68Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated Siglec-9 motif containing peptide (68Ga-DOTA-Siglec-9) could detect inflammatory response due to S. epidermidis peri-implant infection by positron emission tomography (PET).MethodsThirty 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, 68Ga-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.ResultsIn group 3, the tibias with implanted sterile catheters showed an increased local uptake of 68Ga-DOTA-Siglec-9 compared with the intact contralateral bones (SUVratio +29.5%). 68Ga-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.ConclusionPET/CT imaging with novel 68Ga-DOTA-Siglec-9 tracer was able to detect inflammatory tissue response induced by catheter implantation and staphylococcal infections.

Highlights

Staphylococcus epidermidis (S. epidermidis) has emerged as one of the leading pathogens of biomaterial-related infections
We have recently discovered that Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of Vascular adhesion protein-1 (VAP-1) and a Gallium-68-labelled 1,4,7,10-tetraazacyclododecane1,4,7,10-tetraacetic acid (DOTA)-conjugated Siglec-9 motif peptide (68Ga-DOTA-Siglec-9) can be used for positron emission tomography (PET) imaging of inflammation and cancer [21]
There were no significant differences in biofilm mass and, in the capacity of biofilm production between the S. epidermidis and S. aureus strains

Summary

Introduction

Staphylococcus epidermidis (S. epidermidis) has emerged as one of the leading pathogens of biomaterial-related infections. We hypothesized that 68Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated Siglec-9 motif containing peptide (68Ga-DOTA-Siglec-9) could detect inflammatory response due to S. epidermidis peri-implant infection by positron emission tomography (PET). Coagulase-negative staphylococci, including Staphylococcus epidermidis, have emerged as the leading pathogen of nosocomial implant-related infections, including periprosthetic joint infections [1] and intravascular catheterrelated bloodstream infections [2]. The inaccuracy of [18Fluorine]-2-fluoro-2-deoxyglucose combined positron-emission tomography/computed tomography (18F-FDG PET/CT) imaging relates to the high uptake of the tracer both in bacterial infections and aseptic inflammatory processes, such as mechanical loosening of prostheses [12], but probably to the difficulties in detection of indolent low-grade S. epidermidis infections. The result demonstrated the need of better PET tracers for diagnosing S. epidermidis infections

Methods

Results

Conclusion