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

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

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 18...

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Main Authors: 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, Sanjay K. Jain
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61700-6
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Summary: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.
ISSN:2041-1723

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