Abstract
Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of immuno-compromised humans caused by the ubiquitous environmental mold Aspergillus. Biomarker tests for the disease lack sensitivity and specificity, and culture of the fungus from invasive lung biopsy is slow, insensitive, and undesirable in critically ill patients. A computed tomogram (CT) of the chest offers a simple non-intrusive diagnostic procedure for rapid decision making, and so is used in many hematology units to drive antifungal treatment. However, radiological indicators that raise the suspicion of IPA are either transient signs in the early stages of the disease or not specific for Aspergillus infection, with other angio-invasive molds or bacterial pathogens producing comparable radiological manifestations in a chest CT. Improvements to the specificity of radiographic imaging of IPA have been attempted by coupling CT and positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG), a marker of metabolic activity well suited to cancer imaging, but with limited use in invasive fungal disease diagnostics due to its inability to differentiate between infectious etiologies, cancer, and inflammation. Bioluminescence imaging using single genetically modified strains of Aspergillus fumigatus has enabled in vivo monitoring of IPA in animal models of disease. For in vivo detection of Aspergillus lung infections in humans, radiolabeled Aspergillus-specific monoclonal antibodies, and iron siderophores, hold enormous potential for clinical diagnosis. This review examines the different experimental technologies used to image IPA, and recent advances in state-of-the-art molecular imaging of IPA using antibody-guided PET/magnetic resonance imaging (immunoPET/MRI).
Highlights
INTRODUCTIONAlternative techniques for non-invasive imaging of Invasive pulmonary aspergillosis (IPA) have been developed and tested in preclinical animal models of disease (Velde and Wiehr, 2017)
Invasive pulmonary aspergillosis is a frequently fatal lung disease of immuno-compromised individuals caused by inhalation of spores of the air-borne fungus Aspergillus
Radiological imaging of the lung is an attractive means of diagnosing invasive fungal infections since it is a non-invasive procedure, but abnormalities seen in a chest computed tomogram (CT) which are suggestive of Invasive pulmonary aspergillosis (IPA) are not sufficiently specific for definitive diagnosis of the disease
Summary
Alternative techniques for non-invasive imaging of IPA have been developed and tested in preclinical animal models of disease (Velde and Wiehr, 2017) One such method is bioluminescence, that has been used to track Candida albicans and A. fumigatus infections and to monitor their responsiveness to antifungal treatments (Doyle et al, 2006; d’Enfert et al, 2010; Brock, 2012; Jacobsen et al, 2014). Transformed strains of the pathogen have been used to monitor antifungal drug efficacies in vitro and in vivo (Brock et al, 2008; Galiger et al, 2013) and to investigate the roles of resident and recruited immune effector cells in defense against invasive A. fumigatus infections (Ibrahim-Granet et al, 2010) The limitation of this technique is the requirement for genetically modified strains, which restricts studies to single mutants of the pathogen expressing luciferase. The aim of this mini-review is to examine recent advances in molecular imaging of IPA using radiolabeled Aspergillus-specific monoclonal antibodies (mAbs), and iron siderophores, and their potential for translation to the clinical setting
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