Journal article
Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo
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.
Language: | English |
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Publisher: | Ivyspring International Publisher |
Year: | 2017 |
Pages: | 3398-3414 |
ISSN: | 18387640 |
Types: | Journal article |
DOI: | 10.7150/thno.20919 |
ORCIDs: | Fonslet, Jesper and Jensen, Mikael |
Aspergillosis Aspergillus ImmunoPET/MRI Infectious Diseases JF5 Monoclonal Antibody SDG 3 - Good Health and Well-being
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane Acetates Animals Antibodies, Fungal Antibodies, Monoclonal, Humanized Aspergillus nidulans CHO Cells Copper Radioisotopes Cricetinae Cricetulus Female Heterocyclic Compounds, 1-Ring ImmunoPET/MRI. Magnetic Resonance Imaging Mice Mice, Inbred C57BL Positron-Emission Tomography Radiopharmaceuticals