ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo.

Autor: Rolle AM; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, 72076 Tübingen, Germany;, Hasenberg M; Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;, Thornton CR; Biosciences and ISCA Diagnostics Ltd., College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom;, Solouk-Saran D; Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;, Männ L; Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;, Weski J; Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;, Maurer A; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, 72076 Tübingen, Germany;, Fischer E; Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland;, Spycher PR; Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland;, Schibli R; Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland;, Boschetti F; CheMatech, Faculté des Sciences Mirande, 21000 Dijon, France;, Stegemann-Koniszewski S; 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;, Bruder D; 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;, Severin GW; 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;, Autenrieth SE; Department of Hematology, Oncology, Rheumatology, Immunology and Pulmonology, University Hospital Tübingen, 72076 Tübingen, Germany;, Krappmann S; Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany., Davies G; Biosciences and ISCA Diagnostics Ltd., College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom;, Pichler BJ; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, 72076 Tübingen, Germany;, Gunzer M; 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., Wiehr S; 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.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2016 Feb 23; Vol. 113 (8), pp. E1026-33. Date of Electronic Publication: 2016 Jan 19.
DOI: 10.1073/pnas.1518836113
Abstrakt: 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.
Databáze: MEDLINE