Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo
| Autor: | Mikael Jensen, Matthias Gunzer, Philipp R. Spycher, Djamschid Solouk-Saran, Christopher R. Thornton, Mike Hasenberg, Martin Eichner, Bernd J. Pichler, Lauren S. Ryder, Anna-Maria Rolle, Stefan Wiehr, Jesper Fonslet, Adrien Dubois, Roger Schibli, Frédéric Boschetti, Genna Davies, Franck Denat, Claudia Schillinger, Andreas Maurer, Juliane Weski |
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| Přispěvatelé: | College of Life and Environmental Sciences, University of Exeter, Department of Preclinical Imaging and Radiopharmacy [Eberhard Karls University Tübingen], Eberhard Karls University Tübingen, Center for Radiopharmaceutical Sciences, Research Department Biology and Chemistry [Paul Scherrer Institute] ( CRS ), Paul Scherrer Institute ( PSI ), Institute for Experimental Immunology and Imaging [University Hospital of Duisburg-Essen], Universitätsklinikum Essen [Universität Duisburg-Essen] ( Uniklinik Essen ), The Hevesy Laboratory, DTU Nutech [Technical University of Denmark], Technical University of Denmark [Lyngby] ( DTU ), Center for Nanomedicine and Theranostics [Technical University of Denmark], CheMatech - Macrocycle Design Technologies, Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] ( ICMUB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Institute for Clinical Epidemiology and Applied Biometry [Eberhard Karls University Tübingen], European Union 602820 Deutsche Forschungsgemeinschaft WI3777/1-2 Werner Siemens Foundation, Center for Radiopharmaceutical Sciences, Research Department Biology and Chemistry [Paul Scherrer Institute] (CRS), Paul Scherrer Institute (PSI), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Technical University of Denmark [Lyngby] (DTU), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
dota
0301 basic medicine Pathology Monoclonal Antibody Medizin inflammatory diseases Medicine (miscellaneous) ImmunoPET/MRI Acetates Aspergillosis Epitope Aspergillus fumigatus Mice pet/mri Cricetinae Medicine [ SDV.IB ] Life Sciences [q-bio]/Bioengineering Pharmacology Toxicology and Pharmaceutics (miscellaneous) biology Magnetic Resonance Imaging 3. Good health Infectious Diseases Aspergillus [SDV.IB]Life Sciences [q-bio]/Bioengineering Female Antibody reveals Research Paper medicine.medical_specialty medicine.drug_class 030106 microbiology Lung biopsy CHO Cells Monoclonal antibody Antibodies Monoclonal Humanized Aspergillus nidulans 03 medical and health sciences Heterocyclic Compounds 1-Ring Cricetulus SDG 3 - Good Health and Well-being Antigen In vivo [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology galactofuranose Animals Antibodies Fungal JF5 business.industry fumigatus medicine.disease biology.organism_classification Mice Inbred C57BL Copper Radioisotopes Positron-Emission Tomography biology.protein biosynthesis Radiopharmaceuticals business [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Theranostics Theranostics, Ivyspring International Publisher, 2017, 7 (14), pp.3398-3414. 〈http://www.thno.org/v07p3398.htm〉. 〈10.7150/thno.20919〉 Davies, G, Rolle, A-M, Maurer, A, Spycher, P R, Schillinger, C, Solouk-Saran, D, Hasenberg, M, Weski, J, Fonslet, J, Dubois, A, Boschetti, F, Denat, F, Gunzer, M, Eichner, M, Ryder, L S, Jensen, M, Schibli, R, Pichler, B J, Wiehr, S & Thornton, C R 2017, ' Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo ', Theranostics, vol. 7, no. 14, pp. 3398-3414 . https://doi.org/10.7150/thno.20919 Theranostics, 7 (14) Theranostics, Ivyspring International Publisher, 2017, 7 (14), pp.3398-3414. ⟨10.7150/thno.20919⟩ |
| ISSN: | 1838-7640 |
| DOI: | 10.7150/thno.20919〉 |
| Popis: | 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 [64Cu] 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 [64Cu] 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 [64Cu] NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds to the antigenic determinant beta 1,5-galactofuranose (Galf) present in a diagnostic mannoprotein antigen released by the pathogen during invasive growth in the lung. The absence of the epitope Galf in mammalian carbohydrates, coupled with the enhanced imaging capabilities of the hJF5 antibody, means that the [64Cu] NODAGA-hJF5 tracer developed here represents an ideal candidate for the diagnosis of IPA and translation to the clinical setting. |
| Databáze: | OpenAIRE |
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