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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 [(64)Cu]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 [(64)Cu]DOTA-JF5 distinguished IPA from bacterial lung infections and, in contrast to [(18)F]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 noninvasive 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. 

Author information

Rolle AM1, Hasenberg M2, Thornton CR3, Solouk-Saran D2, Männ L2, Weski J2, Maurer A1, Fischer E4, Spycher PR4, Schibli R4, Boschetti F5, Stegemann-Koniszewski S6, Bruder D6, Severin GW7, Autenrieth SE8, Krappmann S9, Davies G3, Pichler BJ1, Gunzer M10, Wiehr S11.​

1Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, 72076 Tübingen, Germany;

2Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;

3Biosciences and ISCA Diagnostics Ltd., College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom;

4Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland;

5CheMatech, Faculté des Sciences Mirande, 21000 Dijon, France;

6Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; Infection Immunology, Institute of Medical Microbiology, Infection Control and Prevention, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany;

7The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark, 4000 Roskilde, Denmark; Center for Nanomedicine and Theranostics, Technical University of Denmark, 2800 Lyngby, Denmark;

8Department of Hematology, Oncology, Rheumatology, Immunology and Pulmonology, University Hospital Tübingen, 72076 Tübingen, Germany;

9Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.

10Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany; stefan.wiehr@med.uni-tuebingen.de matthias.gunzer@uni-due.de.

11Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, 72076 Tübingen, Germany; stefan.wiehr@med.uni-tuebingen.de matthias.gunzer@uni-due.de.