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<p>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 <sup>18</sup>F-fluorodeoxysorbitol (<sup>18</sup>F-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 <sup>18</sup>F-FDS PET signal to infection sites as the primary outcome (NCT05611892). <sup>18</sup>F-FDS PET (120 or 180 min after injection), rapidly detects and localizes invasive pulmonary and cerebral infections due to <i>Aspergillus</i>, non-<i>Aspergillus</i> (galactomannan-negative), or azole-resistant molds, and differentiates them from sterile inflammation or cancer. Moreover, <sup>18</sup>F-FDS selectively and rapidly accumulates intracellularly in a range of clinically relevant molds, including azole-resistant molds, via a saturable process. In animals, <sup>18</sup>F-FDS PET is able to detect and localize pulmonary and cerebral aspergillosis, as well as rhinosinusal infections due to <i>Aspergillus</i>, <i>Rhizopus</i>, and <i>Mucor</i>, confirming the clinical data. <sup>18</sup>F-FDS can be easily synthesized from <sup>18</sup>F-fluorodeoxyglucose (<sup>18</sup>F-FDG), which is widely available, and represents a promising, noninvasive diagnostic tool for detecting, localizing and monitoring of invasive mold infections throughout the body.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月10日

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  • 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

摘要

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.