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68Ga-DOTAVAP-P1 PET imaging capable of demonstrating the phase of inflammation in healing bones and the progress of infection in osteomyelitic bones

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Abstract

Purpose

Differentiation between bacterial infection and nonbacterial inflammation remains a diagnostic challenge. Vascular adhesion protein 1 (VAP-1) is a human endothelial protein whose cell surface expression is induced under inflammatory conditions, thus making it a highly promising target molecule for studying inflammatory processes in vivo. We hypothesized that positron emission tomography (PET) with gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N′,N″,N′′′,N″″-tetraacetic acid-peptide targeted to VAP-1 (68Ga-DOTAVAP-P1) could be feasible for imaging the early inflammatory and infectious processes in healing bones.

Materials and methods

Thirty-four Sprague–Dawley rats with diffuse Staphylococcus aureus tibial osteomyelitis and 34 rats with healing cortical bone defects (representing the inflammation stage of healing) were PET imaged using 68Ga-DOTAVAP-P1 as a tracer. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Bone samples for quantitative bacteriology and specimens were also processed for histomorphometry of inflammatory and infectious reactions.

Results

PET imaging showed an uptake of 68Ga-DOTAVAP-P1 in both the osteomyelitic bones and the healing cortical bone defects during the first 36 h after surgery. Thereafter, only the osteomyelitic tibias were delineated by PET. The osteomyelitic and control animals showed a similar uptake of the 68Ga-DOTAVAP-P1 at 24 h, whereas a significant difference was observed at 7 days (p < 0.0001).

Conclusions

The current study showed that PET imaging with the new 68Ga-DOTAVAP-P1 is capable of accurately demonstrating the phase of inflammation in healing bones and the progress of bacterial infection in osteomyelitic bones. Consequently, this novel imaging agent allowed for the differentiation of bone infection due to S. aureus and normal bone healing as soon as 7 days after onset.

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Acknowledgments

This work was funded by grants from the National Technology Agency of Finland (TEKES), the Academy of Finland (grants No. 205757 and No. 103032), the Instrumentarium Foundation, the Turku University Foundation, the Walter and Lisi Wahl Foundation, and the Finnish Cultural Foundation. Petteri Lankinen is a Ph.D. student supported by the Finnish Graduate School for Musculoskeletal Diseases. Tiina Pöyhönen is a Ph.D. student supported by the Drug Discovery Graduate School of the University of Turku. The authors acknowledge Anni Virolainen-Julkunen, M.D., Ph.D., for conducting the PFGE analysis, and Jouni Alin, M.Sc., for statistical consultation.

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Authors and Affiliations

  1. Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, University of Turku, Turku, Finland

    Petteri Lankinen, Tatu J. Mäkinen & Hannu T. Aro

  2. Turku PET Centre, Turku University Hospital, Turku, Finland

    Tiina A. Pöyhönen, Pauliina Virsu, Satu Salomäki & Anne Roivainen

  3. Department of Chemistry, University of Turku, Turku, Finland

    Satu Salomäki

  4. Department of Bacterial and Inflammatory Diseases, National Public Health Institute, Turku, Finland

    Antti J. Hakanen

  5. MediCity Research Laboratory, University of Turku, Turku, Finland

    Sirpa Jalkanen

  6. National Public Health Institute, Turku, Finland

    Sirpa Jalkanen

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  1. Petteri Lankinen
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Correspondence to Anne Roivainen.

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Lankinen, P., Mäkinen, T.J., Pöyhönen, T.A. et al. 68Ga-DOTAVAP-P1 PET imaging capable of demonstrating the phase of inflammation in healing bones and the progress of infection in osteomyelitic bones. Eur J Nucl Med Mol Imaging 35, 352–364 (2008). https://doi.org/10.1007/s00259-007-0637-5

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  • DOI: https://doi.org/10.1007/s00259-007-0637-5

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