Abstract
Despite increasing associated mortality and morbidity, the diagnosis of fungal infections, especially with Aspergillus fumigatus (A. fumigatus), remains challenging. Based on known ability of Aspergillus species to utilize sorbitol, we evaluated 2-[18F]-fluorodeoxysorbitol (FDS), a recently described Enterobacterales imaging ligand, in animal models of A. fumigatus infection, in comparison with 2-[18F]-fluorodeoxyglucose (FDG). In vitro assays showed slightly higher 3H-sorbitol uptake by live compared with heat-killed A. fumigatus. However, this was 10.6-fold lower than E. coli uptake. FDS positron emission tomography (PET) imaging of A. fumigatus pneumonia showed low uptake in infected lungs compared with FDG (0.290 ± 0.030 vs. 8.416 ± 0.964 %ID/mL). This uptake was higher than controls (0.098 ± 0.008 %ID/mL) and minimally higher than lung inflammation (0.167 ± 0.007 %ID/mL). In the myositis models, FDS uptake was highest in live E. coli infections. Uptake was low in A. fumigatus myositis model and only slightly higher in live compared with the heat-killed side. In conclusion, we found low uptake of 3H-sorbitol and FDS by A. fumigatus cultures and infection models compared with E. coli, likely due to the need for induction of sorbitol dehydrogenase by sorbitol. Our findings do not support FDS as an Aspergillus imaging agent. At this point, FDS remains more selective for imaging Gram-negative Enterobacterales.
Highlights
Publisher’s Note: MDPI stays neutralAspergillus fumigatus (A. fumigatus) is an opportunistic pathogen for immunocompromised subjects
The uptake in A. fumigatus was higher than that seen in J774 macrophages, S. aureus, and P. aeruginosa, which have been previously described as having low FDS uptake [23]
The uptake in C. albicans was slightly higher than in A. fumigatus when normalized to weight from 30 min to 60 min it was lower than A. fumigatus at 120 min (Figure 1A)
Summary
Aspergillus fumigatus (A. fumigatus) is an opportunistic pathogen for immunocompromised subjects. Immunocompetent subjects may inhale up to 1000 conidia each day, those are usually cleared by lung epithelial cells and macrophages [1]. In immunocompromised patients such as those undergoing chemotherapy or organ transplants, on the other hand, fungal conidia can evade the immune system, germinate, and invade lung tissues, resulting in severe and often fatal invasive pulmonary aspergillosis (IPA) [2,3,4]. IPA, for one, has emerged as the leading cause of infectious death in immunocompromised patients [6]. Due to its prevalence and costly treatments, IPA is the most expensive fungal disease [7]
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