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18F-Fluorodeoxysorbitol PET for noninvasive detection of invasive mold infections: preclinical and first-in-human
Carlos E Ruiz-Gonzalez1,2, Oscar J Nino-Meza1,2, Medha Singh1,2
1Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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) in nine prospectively enrolled patients with high-suspicion of invasive mold infections (eventually confirmed using culture or molecular assays, n = 4) or other pathologies (n = 5) with localization of 18F-FDS PET signal to infection sites as the primary outcome (NCT05611892). 18F-FDS PET (120 or 180 min after injection), rapidly detects and localizes invasive pulmonary and cerebral infections due to Aspergillus, non-Aspergillus (galactomannan-negative), or azole-resistant molds, and differentiates them from sterile inflammation or cancer. Moreover, 18F-FDS selectively and rapidly accumulates intracellularly in a range of clinically relevant molds, including azole-resistant molds, via a saturable process. In animals, 18F-FDS PET 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 can be easily synthesized from 18F-fluorodeoxyglucose (18F-FDG), which is widely available, and represents a promising, noninvasive diagnostic tool for detecting, localizing and monitoring of invasive mold infections throughout the body.
Insights
New whole-body positron emission tomography (PET) using 18F-fluorodeoxysorbitol (18F-FDS) effectively detects invasive mold infections. This noninvasive imaging tool rapidly identifies fungal infections, including difficult-to-detect resistant molds, in cancer patients.
Area of Science:
- Medical Imaging
- Infectious Diseases
- Nuclear Medicine
Background:
- Invasive mold infections pose a significant mortality risk for immunosuppressed and cancer patients.
- Current diagnostic methods are often invasive or lack sensitivity, especially for non-Aspergillus or azole-resistant molds.
- There is a critical need for sensitive, noninvasive diagnostic tools for early detection and localization of these infections.
Purpose of the Study:
- To evaluate the efficacy of whole-body 18F-fluorodeoxysorbitol (18F-FDS) positron emission tomography (PET) for detecting and localizing invasive mold infections.
- To assess the ability of 18F-FDS PET to differentiate fungal infections from sterile inflammation or cancer.
- To determine if 18F-FDS PET can detect infections caused by a broad range of molds, including azole-resistant strains.
Main Methods:
- Prospective enrollment of nine patients with high suspicion of invasive mold infections (NCT05611892).
- Whole-body 18F-FDS PET imaging was performed 120 or 180 minutes after injection.
- Infection confirmation was achieved through culture or molecular assays; diagnoses were compared with imaging findings.
Main Results:
- 18F-FDS PET successfully detected and localized invasive pulmonary and cerebral mold infections in confirmed cases.
- The imaging technique differentiated fungal infections from other pathologies like sterile inflammation and cancer.
- 18F-FDS PET demonstrated rapid intracellular accumulation in various molds, including azole-resistant types, and showed efficacy in animal models for aspergillosis and other fungal infections.
- The tracer can be synthesized from readily available 18F-fluorodeoxyglucose (18F-FDG).
Conclusions:
- Whole-body 18F-FDS PET is a promising noninvasive tool for the rapid detection and localization of invasive mold infections.
- This imaging modality offers advantages in identifying infections caused by diverse and resistant fungal species.
- 18F-FDS PET has the potential to improve the diagnosis, monitoring, and management of invasive fungal infections in vulnerable patient populations.
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