Antibody-guided in vivo imaging of Aspergillus fumigatus lung infections during antifungal azole treatment

Sophie Henneberg, Anja Hasenberg, Andreas Maurer, Franziska Neumann, Lea Bornemann, Irene Gonzalez-Menendez, Andreas Kraus, Mike Hasenberg, Christopher R. Thornton, Bernd J. Pichler, Matthias Gunzer () and Nicolas Beziere ()
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Sophie Henneberg: University of Duisburg-Essen
Anja Hasenberg: University of Duisburg-Essen
Andreas Maurer: Eberhard Karls University
Franziska Neumann: University of Duisburg-Essen
Lea Bornemann: University of Duisburg-Essen
Irene Gonzalez-Menendez: Eberhard Karls University
Andreas Kraus: University of Duisburg-Essen
Mike Hasenberg: University of Duisburg-Essen
Christopher R. Thornton: University of Exeter
Bernd J. Pichler: Eberhard Karls University
Matthias Gunzer: University of Duisburg-Essen
Nicolas Beziere: Eberhard Karls University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of immunocompromised humans, caused by the opportunistic fungal pathogen Aspergillus fumigatus. Inadequacies in current diagnostic procedures mean that early diagnosis of the disease, critical to patient survival, remains a major clinical challenge, and is leading to the empiric use of antifungal drugs and emergence of azole resistance. A non-invasive procedure that allows both unambiguous detection of IPA and its response to azole treatment is therefore needed. Here, we show that a humanised Aspergillus-specific monoclonal antibody, dual labelled with a radionuclide and fluorophore, can be used in immunoPET/MRI in vivo in a neutropenic mouse model and 3D light sheet fluorescence microscopy ex vivo in the infected mouse lungs to quantify early A. fumigatus lung infections and to monitor the efficacy of azole therapy. Our antibody-guided approach reveals that early drug intervention is critical to prevent complete invasion of the lungs by the fungus, and demonstrates the power of molecular imaging as a non-invasive procedure for tracking IPA in vivo.

Date: 2021
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DOI: 10.1038/s41467-021-21965-z

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