Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone

Abstract

Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in vitro. We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immunoPET imaging in an in vivo mouse model of prosthetic joint infection (PJI). In vitro and ex vivo binding of the anti-LTA mAb to pathogenic bacteria was measured with Octet, ELISA, and flow cytometry. The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography (PET) with [¹⁸F]FDG and [¹⁸F]NaF as well as X-ray computed tomography (CT), before being evaluated with the zirconium-89-labeled antibody specific for LTA ([⁸⁹Zr]SAC55). The anti-LTA mAb exhibited specific binding in vitro to LTA-expressing bacteria. Results from imaging showed that our model could reliably simulate infection at the surgical site by bioluminescent imaging, conventional PET tracer imaging, and bone morphological changes by CT. One day following injection of both the radiolabeled anti-LTA and isotype control antibodies, the anti-LTA antibody demonstrated significantly greater (P < 0.05) uptake at S. aureus-infected prosthesis sites over either the same antibody at sterile prosthesis sites or of control non-specific antibody at infected prosthesis sites. Taken together, the radiolabeled anti-LTA mAb, [⁸⁹Zr]SAC55, may serve as a valuable diagnostic molecular imaging probe to help distinguish between sterile inflammation and infection in the setting of PJI. Future studies are needed to determine whether these findings will translate to human PJI.

Joint replacements: Distinguishing infection from inflammation

A new imaging technique distinguishes bacterial infection at the site of joint implants from less-serious postoperative inflammation, saving patients from unnecessary and invasive treatments. Daniel Thorek of Johns Hopkins University School of Medicine and colleagues used an antibody that binds to lipoteichoic acid on the cell wall of Staphylococcus bacteria to detect infection at joint implant sites. The antibody was labeled with a radioactive agent and injected into mice that simulated infection of a knee replacement site. A PET scan conducted 1 day after antibody injection showed that it gathered at the infected joint significantly more than it did at the uninfected implant sites in other mice. This method could improve the diagnosis of joint implant infection, which necessitates removal of the prosthetic and all infected tissues, followed by prolonged antibiotic therapy.

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