260. Detection of Aspergillus fumigatus Infection in Mice with 2-Deoxy-2-[18F]fluorosorbitol

Abstract

BackgroundInvasive aspergillosis is a major cause of infectious morbidity and mortality in immunocompromised patients.However, definitive diagnosis of invasive Aspergillus infection is still difficult due to the lack of a rapid, sensitive and specific diagnostic methods. In this studies, we investigated 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS) which has been reported to be accumulated in Gram-negative bacteria but not in Gram-positive bacteria or healthy mammalian or cancer cells, for the imaging detection of Aspergullus fumigatus 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. The probe uptake assay was performed by incubating bacterial cell and fungi with [18F]FDS (20 µCi) at 37°C for 2 h. Female BALB/c were immunosuppressed with cyclophosphamide and cortisone acetate prior to A. fumigatus intranasal, intramuscular, brain infection. The mircoPET images were obtained at 2 h after i.v. injection of [18F]FDS in infected mice.ResultsIn vitro uptake test revealed significantly higher accumulation of [18F]FDS at 2 hin A. fumigatus, C. albicans and R. oryzae rather than with bacterial strains (Figure 1). PET imaging of BALB/c mice with pulmonary A. fumigatus infections showed obvious accumulation of [18F]FDS in the infected lungs compared with control (Figure 2). [18F]FDS PET imaging also detected A. fumigatus muscle and brain infection in mice. In infected shoulder muscle of mice, [18F]FDS PET imaging showed high legion-to-background ratio at 2 h. (4.05 ± 1.59, Figure 3).Conclusion[18F]FDS PET study demonstrated stable uptake in infected tissue with A. fumigatus and rapid clearance from the blood and other organs. [18F]FDS could be a useful imaging probe visualizing the invasive aspergillosis in vivo. Disclosures All authors: No reported disclosures.