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.

Results from the nanoScan^® PET/CT

• Authors found low selectivity for FDS in A. fumigatus.
• Although A. fumigatus can accumulate FDS to a limited extent, the uptake is very low both in vitro and in vivo, and therefore, FDS is not a viable ligand for PET imaging of A. fumigatus infections.

Figure 4. Static 18F-fluorodeoxyglucose (FDG) and 2-[18F]-fluorodeoxysorbitol (FDS) PET/CT imaging of E. coli, S. aureus, and A. fumigatus myositis models. (A) Maximum intensity projections (MIPs) of representative PET/CT images and (B) quantified uptake values (%ID/mL) show high FDG uptake in both live (orange arrows) and heat-killed injection sites (blue arrows) in all three models. FDS uptake, on the other hand, is highest in association with live E. coli with no appreciable uptake seen on the heat-killed side. S. aureus and A. fumigatus models show higher FDS uptake in the live versus heat-killed (HK) thighs, however, the uptake associated with live infection is much lower than that seen in live E. coli model.

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