TY - JOUR
T1 - Immuno PET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo
AU - Rolle, Anna-Maria
AU - Hasenberg, Mike
AU - Thornton, Christopher R.
AU - Solouk-Saran, Djamschid
AU - Mann, Linda
AU - Weski, Juliane
AU - Maurer, Andreas
AU - Fischer, Eliane
AU - Spycher, Philipp R.
AU - Schibli, Roger
AU - Boschetti, Frederic
AU - Stegemann-Koniszewski, Sabine
AU - Bruder, Dunja
AU - Severin, Gregory W.
AU - Autenrieth, Stella E.
AU - Krappmann, Sven
AU - Davies, Genna
AU - Pichler, Bernd J.
AU - Gunzer, Matthias
AU - Wiehr, Stefan
PY - 2016
Y1 - 2016
N2 - 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 [64Cu]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 [64Cu]DOTA-JF5 distinguishedIPA from bacterial lung infections and, in contrast to [18F]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 non-invasive 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.
AB - 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 [64Cu]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 [64Cu]DOTA-JF5 distinguishedIPA from bacterial lung infections and, in contrast to [18F]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 non-invasive 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.
KW - Aspergillus fumigatus
KW - Aspergillosis
KW - ImmunoPET/MR
KW - PET
KW - Imaging
U2 - 10.1073/pnas.1518836113
DO - 10.1073/pnas.1518836113
M3 - Journal article
C2 - 26787852
SN - 0027-8424
VL - 113
SP - E1026-E1033
JO - Proceedings of the National Academy of Sciences
JF - Proceedings of the National Academy of Sciences
IS - 8
ER -
