Immuno PET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo

Anna-Maria Rolle, Mike Hasenberg, Christopher R. Thornton, Djamschid Solouk-Saran, Linda Mann, Juliane Weski, Andreas Maurer, Eliane Fischer, Philipp R. Spycher, Roger Schibli, Frederic Boschetti, Sabine Stegemann-Koniszewski, Dunja Bruder, Gregory W. Severin, Stella E. Autenrieth, Sven Krappmann, Genna Davies, Bernd J. Pichler, Matthias Gunzer, Stefan Wiehr

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    Abstract

    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and tested a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging.Administration of a [64Cu]DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus-infected mice allowed specific localization of lung infection when combined with PET. Optical imaging with a fluorochrome-labeled version of the mAb showed colocalization with invasive hyphae. The mAb-based newly developed PET tracer [64Cu]DOTA-JF5 distinguishedIPA from bacterial lung infections and, in contrast to [18F]FDG-PET, discriminated IPA from a general increase in metabolic activity associated with lung inflammation. To our knowledge, this is the first time that antibody-guided in vivo imaging has been used for non-invasive diagnosis of a fungal lung disease (IPA) of humans, an approach with enormous potential for diagnosis of infectious diseases and with potential for clinical translation.
    Original languageEnglish
    JournalProceedings of the National Academy of Sciences
    Volume113
    Issue number8
    Pages (from-to)E1026-E1033
    ISSN0027-8424
    DOIs
    Publication statusPublished - 2016

    Keywords

    • Aspergillus fumigatus
    • Aspergillosis
    • ImmunoPET/MR
    • PET
    • Imaging

    Cite this

    Rolle, A-M., Hasenberg, M., Thornton, C. R., Solouk-Saran, D., Mann, L., Weski, J., Maurer, A., Fischer, E., Spycher, P. R., Schibli, R., Boschetti, F., Stegemann-Koniszewski, S., Bruder, D., Severin, G. W., Autenrieth, S. E., Krappmann, S., Davies, G., Pichler, B. J., Gunzer, M., & Wiehr, S. (2016). Immuno PET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo. Proceedings of the National Academy of Sciences, 113(8), E1026-E1033. https://doi.org/10.1073/pnas.1518836113