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Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Advances in the In Vivo Molecular Imaging of Invasive Aspergillosis
Matthias Gunzer1,2, Christopher R Thornton3, Nicolas Beziere4
1Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, 45147 Essen, Germany.
Abstract:
Invasive pulmonary aspergillosis (IPA) is a life-threatening infection of immunocompromised patients with Aspergillus fumigatus, a ubiquitous environmental mould. While there are numerous functioning antifungal therapies, their high cost, substantial side effects and fear of overt resistance development preclude permanent prophylactic medication of risk-patients. Hence, a fast and definitive diagnosis of IPA is desirable, to quickly identify those patients that really require aggressive antimycotic treatment and to follow the course of the therapeutic intervention. However, despite decades of research into this issue, such a diagnostic procedure is still not available. Here, we discuss the array of currently available methods for IPA detection and their limits. We then show that molecular imaging using positron emission tomography (PET) combined with morphological computed tomography or magnetic imaging is highly promising to become a future non-invasive approach for IPA diagnosis and therapy monitoring, albeit still requiring thorough validation and relying on further acceptance and dissemination of the approach. Thereby, our approach using the A. fumigatus-specific humanized monoclonal antibody hJF5 labelled with 64Cu as PET-tracer has proven highly effective in pre-clinical models and hence bears high potential for human application.
Insights
Diagnosing invasive pulmonary aspergillosis (IPA) is challenging. A novel positron emission tomography (PET) imaging approach using a radiolabeled antibody shows promise for non-invasive IPA detection and monitoring in immunocompromised patients.
Area of Science:
- Medical imaging
- Infectious diseases
- Immunology
Background:
- Invasive pulmonary aspergillosis (IPA) is a severe fungal infection in immunocompromised individuals, often caused by Aspergillus fumigatus.
- Current antifungal therapies are limited by cost, side effects, and resistance, necessitating improved diagnostic methods for targeted treatment.
- Existing diagnostic procedures for IPA lack the speed and definitiveness required for timely clinical intervention.
Purpose of the Study:
- To review current diagnostic methods for IPA and their limitations.
- To evaluate the potential of molecular imaging, specifically positron emission tomography (PET), for non-invasive IPA diagnosis and therapy monitoring.
- To present a novel PET-based approach using a specific antibody tracer for Aspergillus fumigatus detection.
Main Methods:
- Review of existing diagnostic techniques for invasive pulmonary aspergillosis.
- Exploration of positron emission tomography (PET) combined with computed tomography (CT) or magnetic resonance imaging (MRI) for molecular imaging.
- Development and preclinical testing of a 64Cu-labeled humanized monoclonal antibody (hJF5) targeting Aspergillus fumigatus.
Main Results:
- Current IPA diagnostic methods have significant limitations in speed and accuracy.
- Molecular imaging with PET-CT or PET-MRI presents a promising non-invasive strategy for IPA diagnosis and treatment monitoring.
- The 64Cu-labeled hJF5 antibody demonstrated high efficacy in preclinical models for detecting Aspergillus fumigatus.
Conclusions:
- A definitive, rapid diagnostic method for IPA is still needed.
- Molecular imaging, particularly PET, holds significant potential for improving IPA diagnosis and therapy management.
- The developed 64Cu-hJF5 PET tracer shows strong potential for clinical application in diagnosing and monitoring IPA.

