Preclinical evaluation of 2-[18F]fluorodeoxysorbitol as a tracer for targeted imaging of Enterobacterales infection

Fluorine-18-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (¹⁸F-FDG-PET) is widely used for the detection of inflammatory and infectious diseases. Although this modality has proven to be a useful diagnostic tool, reliable distinction of bacterial infection from sterile inflammation or even from a malignancy remains challenging. Therefore, there is a need for bacteria-specific tracers for PET imaging that facilitate a reliable distinction of bacterial infection from other pathology. The present study was aimed at exploring the potential of 2-[¹⁸F]-fluorodeoxysorbitol ([¹⁸F]FDS) as a tracer for detection of Enterobacterales infections. Sorbitol is a sugar alcohol that is commonly metabolized by bacteria of the Enterobacterales order, but not by mammalian cells, which makes it an attractive candidate for targeted bacterial imaging. The latter is important in view of the serious clinical implications of infections caused by Enterobacterales. Here we demonstrate that sorbitol-based PET can be applied to detect a broad range of clinical bacterial isolates not only in vitro, but also in blood and ascites samples from patients suffering from Enterobacterales infections. Notably, the possible application of [¹⁸F]FDS is not limited to Enterobacterales since Pseudomonas aeruginosa and Corynebacterium jeikeium also showed substantial uptake of this tracer. We conclude that [¹⁸F]FDS is a promising tracer for PET-imaging of infections caused by a group of bacteria that can cause serious invasive disease.