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For people with weakened immune systems, invasive pulmonary aspergillosis, a fungal infection of the lungs, poses a great danger. The diagnosis of the infection is often difficult and inaccurate, and the highly invasive procedures are uncomfortable for the already weakened patients. In search of a new diagnostic procedure, the University Hospital of Tübingen joined forces with the University of Duisburg-Essen and the College of Life & Environmental Sciences at the University of Exeter to examine a new antibody-driven imaging method. The study of the approach was conducted using a mouse model and will be used to prepare a clinical translation.
Aspergillus is a common mold readily found worldwide in a variety of environments and can easily be inhaled in everyday life. For healthy people, the spores pose no threat; the immune system fends off the danger. However, in immunocompromised people, the fungus can infect the lungs and cause invasive pulmonary aspergillosis, a rapidly developing fungal infection with a mortality rate of more than 60 percent. For COVID-19 patients admitted in intensive care units in particular, the infection has become a significant problem – an estimated 30 percent of them develop COVID-associated pulmonary aspergillosis.
Managing the fungal infection is difficult because the disease cannot be diagnosed accurately or rapidly. To date, physicians have relied on highly invasive techniques such as lung biopsies or broncho-alveolar lavages (fluid is injected directly into the lungs through the nose or mouth) to make the diagnosis. Although high-resolution X-ray imaging (CT scans) has become more common, lack of specificity means that the suspicion of an infection must still be confirmed using invasive techniques. In debilitated patients, the risks and inconvenience only add to the severity of the disease, so medications are often administered before a conclusive diagnosis can be reached.
In order to develop a quicker, more specific and more convenient diagnostic procedure – capitalizing on the possibilities offered by modern imaging techniques – researchers from the Department of Preclinical Imaging and Radiopharmacy at the Medical Faculty of the University Hospital Tübingen have conducted a study in collaboration with the University of Duisburg-Essen and the College of Life & Environmental Sciences at the University of Exeter. The results are currently published in the journal Nature Communications.
In the study using a mouse model, the researchers were able to show that the hJF5 antibody developed at the University of Exeter can specifically and rapidly recognize the infection in the lungs of infected animals. Using an hJF5-based radiotracer injected only intravenously, advanced molecular imaging techniques developed at the University of Tübingen (combined positron emission tomography and magnetic resonance imaging, PET/MR) were able to provide a rapid and specific diagnosis of the disease while allowing for precise monitoring of the therapy. The imaging results could then be complemented by 3D microscopy performed at the University of Duisburg-Essen, which underlined the accuracy of the developed imaging method with a precise (quantitative) evaluation of the infection. This innovative dual approach proved that all sites of infection could be accurately uncovered, a crucial step to not only provide an estimate of the severity of the infection, but also as a first step in monitoring the success of its therapy. The researchers demonstrated the potential of the therapy monitoring using molecular imaging and the administration of a classical antifungal drug, Voriconazole.
As a next step, the researchers are preparing the clinical translation of the approach. "We strongly expect," says Dr. Nicolas Beziere of the Department of Preclinical Imaging and Radiopharmacy at Tübingen University Hospital and senior author of the study, "that the performance of the newly developed radiotracer will be similar in humans and hope that future clinical trials will show a highly positive impact on survivability with a far lower risk and higher comfort for the patient."
University Hospital Tübingen
University Department of Radiology
Department of Preclinical Imaging and Radiopharmacy
Dr. Nicolas Beziere
Tel. 07071 29-87511
nicolas.beziere@med.uni-tuebingen.de
Antibody-guided in vivo imaging of Aspergillus fumigatus lung infections during anti-fungal azole treatment; DOI: 10.1038/s41467-021-21965-z
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