Comparative evaluation of carbohydrate-based PET tracers for Aspergillus fumigatus imaging

Abstract Background Invasive fungal infections remain a major health concern in immunocompromised patients due to late and unspecific diagnosis. Pathogen-specific Positron Emission Tomography (PET) radiotracers such as 2-deoxy-2-[ 18 F]fluorocellobiose (FCB) and 2-deoxy-2-[ 18 F]fluorosorbitol (FDS) have shown potential to distinguish infections. Based on promising in vitro results with L-Rhamnose, we developed 2-deoxy-2-[ 18 F]fluoro-L-Rhamnose (F-Rham) as a potential fungal specific ligand. However, direct comparisons across tracers are limited by inconsistent experimental conditions in different institutions. Here, we compared FCB, FDS, F-Rham and 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) in identical Aspergillus fumigatus ( A. fumigatus ) animal models and compared FCB and FDS performance in identical bacterial animal models. Results Among the four tested tracers, FCB showed the highest uptake in A. fumigatus in vitro and the highest target-to-non-target ratios in PET imaging of the same murine A. fumigatus myositis model. Unlike FDG, FCB distinguished live infection from heat-killed inoculations. F-Rham did not show specific accumulation at either the live or heat-killed inoculation sites. When comparing FDS and FCB, FCB uptake was higher in A. fumigatus compared to bacterial infections ( Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus )), whereas FDS preferentially accumulated in E. coli , both in vitro and in vivo. Conclusions FCB shows highest accumulation in live A. fumigatus infection, while FDS was preferably taken up by E. coli . Among the tested tracers, FCB showed the most promise for successful detection of live A. fumigatus infection when translated to humans.