18F-Fluorodeoxysorbitol PET for noninvasive detection of invasive mold infections: preclinical and first-in-human studies

Carlos E. Ruiz-Gonzalez, Oscar J. Nino-Meza, Medha Singh, Yuderleys Masias-Leon, Amy Kronenberg, Madelynn Shambles, Xueyi Chen, Elizabeth W. Tucker, Martin A. Lodge, Laurence S. Carroll, Kenneth R. Cooke, Olivia S. Kates, Shmuel Shoham, Sean X. Zhang () and Sanjay K. Jain ()
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Carlos E. Ruiz-Gonzalez: Johns Hopkins University School of Medicine
Oscar J. Nino-Meza: Johns Hopkins University School of Medicine
Medha Singh: Johns Hopkins University School of Medicine
Yuderleys Masias-Leon: Johns Hopkins University School of Medicine
Amy Kronenberg: Johns Hopkins University School of Medicine
Madelynn Shambles: Johns Hopkins University School of Medicine
Xueyi Chen: Johns Hopkins University School of Medicine
Elizabeth W. Tucker: Johns Hopkins University School of Medicine
Martin A. Lodge: Johns Hopkins University School of Medicine
Laurence S. Carroll: Johns Hopkins University School of Medicine
Kenneth R. Cooke: Johns Hopkins University School of Medicine
Olivia S. Kates: Johns Hopkins University School of Medicine
Shmuel Shoham: Johns Hopkins University School of Medicine
Sean X. Zhang: Johns Hopkins University School of Medicine
Sanjay K. Jain: Johns Hopkins University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61700-6

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