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

Pickett, Julie E.; Thompson, John M.; Sadowska, Agnieszka; Tkaczyk, Christine; Sellman, Bret R.; Minola, Andrea; Corti, Davide; Lanzavecchia, Antonio; Miller, Lloyd S.; Thorek, Daniel LJ

doi:10.1038/s41413-018-0014-y

Back

Journal article

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

Pickett, Julie E. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Gaithersburg, MD, USA
Thompson, John M. Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Sadowska, Agnieszka Department of Infectious Disease, MedImmune LLC, Gaithersburg, MD, USA
Tkaczyk, Christine Department of Infectious Disease, MedImmune LLC, Gaithersburg, MD, USA
Sellman, Bret R. Department of Infectious Disease, MedImmune LLC, Gaithersburg, MD, USA
Minola, Andrea Humabs BioMed SA, Bellinzona, Switzerland
Corti, Davide Humabs BioMed SA, Bellinzona, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Miller, Lloyd S. Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA - Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA - Division of Infectious Disease, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Thorek, Daniel LJ Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Gaithersburg, MD, USA - Cancer Molecular and Functional Imaging Program, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

25.04.2018

Published in:

Bone research. - 2018, vol. 6, p. 13

English 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.

Language