Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo .

Autor:	Davies G; ISCA Diagnostics Ltd. and Biosciences, College of Life & Environmental Sciences, University of Exeter, Exeter, United Kingdom., Rolle AM; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany., Maurer A; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany., Spycher PR; Paul Scherrer Institute, Research Department Biology and Chemistry, Center for Radiopharmaceutical Sciences (CRS), Switzerland., Schillinger C; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany., Solouk-Saran D; Institute for Experimental Immunology and Imaging, University Hospital, University of Duisburg-Essen, Essen, Germany., Hasenberg M; Institute for Experimental Immunology and Imaging, University Hospital, University of Duisburg-Essen, Essen, Germany., Weski J; Institute for Experimental Immunology and Imaging, University Hospital, University of Duisburg-Essen, Essen, Germany., Fonslet J; The Hevesy Laboratory, DTU Nutech, Technical University of Denmark.; Center for Nanomedicine and Theranostics, Technical University of Denmark., Dubois A; CheMatech, Faculté des Sciences Mirande, Dijon, France., Boschetti F; CheMatech, Faculté des Sciences Mirande, Dijon, France., Denat F; Institut de Chimie Moléculaire, Université de Bourgogne, Dijon, France., Gunzer M; Institute for Experimental Immunology and Imaging, University Hospital, University of Duisburg-Essen, Essen, Germany., Eichner M; Institute for Clinical Epidemiology and Applied Biometry, Eberhard Karls University Tübingen, Germany., Ryder LS; ISCA Diagnostics Ltd. and Biosciences, College of Life & Environmental Sciences, University of Exeter, Exeter, United Kingdom., Jensen M; The Hevesy Laboratory, DTU Nutech, Technical University of Denmark.; Center for Nanomedicine and Theranostics, Technical University of Denmark., Schibli R; Paul Scherrer Institute, Research Department Biology and Chemistry, Center for Radiopharmaceutical Sciences (CRS), Switzerland., Pichler BJ; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany., Wiehr S; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany., Thornton CR; ISCA Diagnostics Ltd. and Biosciences, College of Life & Environmental Sciences, University of Exeter, Exeter, United Kingdom.
Jazyk:	angličtina
Zdroj:	Theranostics [Theranostics] 2017 Aug 11; Vol. 7 (14), pp. 3398-3414. Date of Electronic Publication: 2017 Aug 11 (Print Publication: 2017).
DOI:	10.7150/thno.20919
Abstrakt:	Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus . Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [ 64 Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus . To enable translation of the tracer to the clinical setting, we report here the development of a humanised version of the antibody (hJF5), and pre-clinical imaging of lung infection using a [ 64 Cu]NODAGA-hJF5 tracer. The humanised antibody tracer shows a significant increase in in vivo biodistribution in A. fumigatus infected lungs compared to its radiolabeled murine counterpart [ 64 Cu]NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds to the antigenic determinant β1,5-galactofuranose (Gal f ) present in a diagnostic mannoprotein antigen released by the pathogen during invasive growth in the lung. The absence of the epitope Gal f in mammalian carbohydrates, coupled with the enhanced imaging capabilities of the hJF5 antibody, means that the [ 64 Cu]NODAGA-hJF5 tracer developed here represents an ideal candidate for the diagnosis of IPA and translation to the clinical setting. Competing Interests: Competing Interests: B.J.P. receives grant/research support from: Bayer Healthcare, Boehringer-Ingelheim, and Siemens; however, none of the grants are directly related to this work. C.R.T. is director of ISCA Diagnostics Ltd.
Databáze:	MEDLINE
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