Abstract
1394
Objectives: Despite the success of effective therapy against fungal infection, it still remains one of the main causes of death in patients with advanced immune suppression. To maximize clinical outcome, the early and accurate diagnosis of infectious diseases is very important. However, the current diagnostic methods depend on blood culture and antigen-based techniques that need time consuming process. Consequently, these techniques lead delayed initiation of therapies and often result in poor outcome. In this studies, we suggest 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS) which has been reported to show uptake in Gram-negative bacteria, for specific detection of fungal infections with PET in vivo.
Methods: [18F]FDS was synthesized by reduction of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) using NaBH4. When the reaction was complete, the mixture was adjusted to a pH value to 6.5-7.5. Subsequently, the solution was filtered directly into a sterile product vial through a Sep-Pak Alumina N cartridge with a sterile filter. Escherichia coli (positive control), Staphylococcus aureus (negative control), Aspergillus fumigatus, Candida albicans and Rhizopus oryzae were aerobically grown and a number of each strain was counted. The probe uptake assay was performed by incubating fungi (1 × 106) with [18F]FDS (20 µCi) at 37°C for 2 h. Immunocompromised nude mice were used to establish fungal infection animal models (lung, shoulder muscle and brain infection with A. fumigatus). The mircoPET images were obtained at 2 h after i.v. injection of [18F]FDS in established animal models.
Results: [18F]FDS was synthesized easily and non-decay corrected radiochemical yield was around 40 %. With only one peak based on radio-TLC reader with Rf = 0.65 - 0.7 (80% acetonitrile with 20% water as eluent, Rf = 0.85 - 0.9 for [18F]FDG). [18F]FDS uptake test revealed significantly higher accumulation at 2 h after incubation with Aspergillus fumigatus, Candida albicans and Rhizopus oryzae rather than with bacterial strains. [18F]FDS PET imaging confirmed specific targeting of Aspergillus fumigatus in infected lung, shoulder muscle or brain in mouse models. For example, [18F]FDS PET imaging demonstated increased uptake in infected shoulder muscle with high legion-to-background ratio at 2 h. (4.05 ± 1.59, Figure. 1).Conclusion: [18F]FDS PET study demonstrated stable uptake in infected tissue with Aspergillus fumigatus and rapid clearance from the blood and other organs. [18F]FDS may be a useful imaging agent that allows visualization of fungal infection in vivo.