18F-Fluorodeoxysorbitol PET for Noninvasive Detection of Invasive Mold Infections in Patients

Abstract Invasive mold infections are a major cause of mortality in immunosuppressed and cancer patients. Diagnosis is challenging, requiring invasive procedures or reliance on fungal biomarkers with limited sensitivity and an inability to detect non-Aspergillus molds. Here, we perform whole-body 18F-fluorodeoxysorbitol (18F-FDS) positron emission tomography (PET) and computed tomography (CT) in nine prospectively enrolled patients with high-suspicion of invasive mold infections (eventually confirmed using culture or molecular assays) or other pathologies (NCT05611892). 18F-FDS PET/CT is safe and can rapidly detect and localize invasive pulmonary and cerebral infections due to Aspergillus, non-Aspergillus (galactomannan-negative), or azole-resistant (Aspergillus calidoustus) molds, and differentiate them from sterile inflammation or cancer. Moreover, 18F-FDS selectively and rapidly accumulates intracellularly in a wide range of clinically relevant molds, including azole-resistant molds, via a saturable process. Tissue histology from eight patients with invasive mold infections demonstrates that lesional biomass occupied by molds is ~50-fold higher than for bacterial infections. In animals, 18F-FDS PET/CT is able to detect and localize pulmonary and cerebral aspergillosis, as well as rhinosinusal infections due to Aspergillus, Rhizopus, and Mucor, confirming the clinical data. 18F-FDS PET represents a promising, noninvasive diagnostic tool for the detection and localization of invasive mold infections throughout the body.