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Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E1026-33. doi: 10.1073/pnas.1518836113. Epub 2016 Jan 19.

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

Author information

1
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, 72076 Tübingen, Germany;
2
Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45122 Essen, Germany;
3
Biosciences and ISCA Diagnostics Ltd., College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom;
4
Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland;
5
CheMatech, Faculté des Sciences Mirande, 21000 Dijon, France;
6
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;
7
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;
8
Department of Hematology, Oncology, Rheumatology, Immunology and Pulmonology, University Hospital Tübingen, 72076 Tübingen, Germany;
9
Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.
10
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.
11
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.

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.

KEYWORDS:

Aspergillus fumigatus; PET; aspergillosis; imaging; immunoPET/MR

PMID:
26787852
PMCID:
PMC4776455
DOI:
10.1073/pnas.1518836113
[Indexed for MEDLINE]
Free PMC Article

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