title: ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo.
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.
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, 72076 Tübingen, Germany;
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Rolle
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;
authors.forename: Mike
authors.initials: M
authors.lastname: Hasenberg
authors.affiliation: Biosciences and ISCA Diagnostics Ltd., College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom;
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Thornton
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;
authors.forename: Djamschid
authors.initials: D
authors.lastname: Solouk-Saran
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;
authors.forename: Linda
authors.initials: L
authors.lastname: Männ
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;
authors.forename: Juliane
authors.initials: J
authors.lastname: Weski
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, 72076 Tübingen, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Maurer
authors.affiliation: Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland;
authors.forename: Eliane
authors.initials: E
authors.lastname: Fischer
authors.affiliation: Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland;
authors.forename: Philipp R
authors.initials: PR
authors.lastname: Spycher
authors.affiliation: Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland;
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.affiliation: CheMatech, Faculté des Sciences Mirande, 21000 Dijon, France;
authors.forename: Frederic
authors.initials: F
authors.lastname: Boschetti
authors.affiliation: Immune 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;
authors.forename: Sabine
authors.initials: S
authors.lastname: Stegemann-Koniszewski
authors.affiliation: Immune 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;
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
authors.affiliation: The 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;
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Severin
authors.affiliation: Department of Hematology, Oncology, Rheumatology, Immunology and Pulmonology, University Hospital Tübingen, 72076 Tübingen, Germany;
authors.forename: Stella E
authors.initials: SE
authors.lastname: Autenrieth
authors.affiliation: Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Krappmann
authors.affiliation: Biosciences and ISCA Diagnostics Ltd., College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom;
authors.forename: Genna
authors.initials: G
authors.lastname: Davies
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, 72076 Tübingen, Germany;
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.affiliation: Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany; stefan.wiehr@med.uni-tuebingen.de matthias.gunzer@uni-due.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gunzer
authors.affiliation: Werner 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.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiehr
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D001232:Aspergillus fumigatus; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D055732:Pulmonary Aspergillosis / Q000000981:diagnostic imaging*; D011859:Radiography
chemical_list: D000908:Antibodies, Fungal; D058846:Antibodies, Monoclonal, Murine-Derived
keywords: Aspergillus fumigatus; PET; aspergillosis; imaging; immunoPET/MR