Ahtinen Helena, Kulkova Julia, Lindholm Laura, Eerola Erkki, Hakanen Antti J, Moritz Niko, Söderström Mirva, Saanijoki Tiina, Jalkanen Sirpa, Roivainen Anne, Aro Hannu T
Turku PET Centre, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, Turku University Hospital, University of Turku, Turku FI-20521, Finland.
EJNMMI Res. 2014 Aug 8;4:45. doi: 10.1186/s13550-014-0045-3. eCollection 2014.
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).
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.
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.
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.
表皮葡萄球菌已成为生物材料相关感染的主要病原体之一。血管黏附蛋白-1（VAP-1）是一种炎症诱导性内皮分子，可控制白细胞外渗。唾液酸结合免疫球蛋白样凝集素9（Siglec-9）是VAP-1的白细胞配体。我们推测，（68）镓标记的1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸偶联的含Siglec-9基序的肽（（68）Ga-DOTA-Siglec-9）可通过正电子发射断层扫描（PET）检测表皮葡萄球菌植入物周围感染引起的炎症反应。
将30只Sprague-Dawley大鼠随机分为三组。将无菌导管植入左胫骨骨髓腔。在第1组和第2组中，植入后在植入物周围注射表皮葡萄球菌或金黄色葡萄球菌，并辅助注射鱼肝油酸钠。在第3组中，注射无菌生理盐水代替细菌，且不使用鱼肝油酸钠。术后2周，进行（68）Ga-DOTA-Siglec-9 PET联合计算机断层扫描（CT），并测量标准化摄取值（SUV）。通过微生物分析、荧光显微镜成像和组织学检查来证实植入物相关感染的存在。体内PET结果通过γ计数器进行体外测量来验证。
在第3组中，植入无菌导管的胫骨与对侧完整骨骼相比，（68）Ga-DOTA-Siglec-9的局部摄取增加（SUV比值增加29.5%）。（68）Ga-DOTA-Siglec-9 PET检测到表皮葡萄球菌和金黄色葡萄球菌导管相关骨感染引起的炎症（SUV比值分别增加58.1%和41.7%）。表皮葡萄球菌组的示踪剂摄取显著高于未接种细菌的第3组，但表皮葡萄球菌组和金黄色葡萄球菌组之间的差异无统计学意义。金黄色葡萄球菌组与第3组之间的差异也无统计学意义。
使用新型（68）Ga-DOTA-Siglec-9示踪剂的PET/CT成像能够检测导管植入和葡萄球菌感染引起的炎症组织反应。
