Multimodal preclinical imaging of aspergillus fumigatus invasion and treatment

Aspergillus fumigatus (A. fumigatus) is a ubiquitous mold whose airborne spores are frequently inhaled. While immunocompetent individuals rarely suffer from related infections, those with compromised immune systems, especially a lack in innate immunity delivered by neutrophils, develop invasive aspergillosis (IA), a severe lung infection. It has a mortality rate of over 40% which is a direct result of the lack of specific diagnosis options. The current Gold Standard is a galactomannan Aspergillus antigen (GM) assay relying on invasive broncho-alveolar lavages (BAL) which only has a specificity of 77%. This finally leads to wrong treatment approaches which usually concentrate on pulmonary tract infections caused by bacteria or viruses that show the same symptoms as an IA. If the fungal infection is treated too late, this leads to a drastically impaired outcome for patients. Hence, to decrease the mortality of IA, a sensitive, specific and quantitative diagnostic tool is needed.

One way to approach this subject is using techniques such as Positron Emission Tomography (PET), as it is already used in oncology. We aim to combine PET with radiolabeled antibodies that bind to a specific mannoprotein in the hyphae of A. fumigatus. Our approach is based on the A. fumigatus specific antibody (JF5) developed by C. Thornton that we mutated to enhance its specificity. Thereby we provided critical new insight on JF5-based in vivo imaging of A. fumigatus and the in vivo diagnosis of the infection in a preclinical model using neutropenic mice infected with A. fumigatus. The project continues to improve the specificity and speed of detection of IA-PET with the goal of developing a highly reliable, fast and non-invasive approach to reach a definitive diagnosis of IA in the affected patients.

Researcher:

• Prof. Dr. Matthias Gunzer
• Lea Allerchen