A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system
Reactive oxygen and nitrogen species (RONS) contribute to the pathogenesis of neurodegeneration, but the inability to detect RONS in vivo in the central nervous system has confounded the interpretation of results of clinical trials of antioxidants. Here we report the synthesis and characterization of a positron emission tomography (PET) probe, [<sup>18</sup>F]fluoroedaravone ([<sup>18</sup>F]FEDV), for the in vivo quantification of oxidative stress. Derived from the antioxidant edaravone, the probe can diffuse through the blood-brain barrier and is stable in human plasma. In mice, PET imaging with [<sup>18</sup>F]FEDV allowed for the detection of RONS after intrastriatal injection of sodium nitroprusside, in the middle cerebral artery after stroke by photothrombosis, and in brains with tauopathy. When using dynamic PET imaging coupled with parametric mapping, the sensitivity of [<sup>18</sup>F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [<sup>18</sup>F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants.
Authors
- Zhongxiao Fu (ORCID: https://orcid.org/0000-0002-8850-6991)
- Kiel D. Neumann (ORCID: https://orcid.org/0000-0001-9093-3522)
- Melissa M. Kinkaid
- James R. Stone (ORCID: https://orcid.org/0000-0001-9122-3311)
- Bijoy Kundu (ORCID: https://orcid.org/0000-0003-2683-9165)
- Herbert Sheppard
- Spenser R. Simpson
- Zoraiz Qureshi (ORCID: https://orcid.org/0000-0003-3905-5490)
- William Terrell
- Paola Villanueva (ORCID: https://orcid.org/0000-0002-6504-2979)
- Emily Bian (ORCID: https://orcid.org/0000-0001-8367-5895)
- Justin H. Wilde (ORCID: https://orcid.org/0000-0001-6076-5484)
- Yu Sun (ORCID: https://orcid.org/0000-0002-6608-1347)
- Saavidra Perera (ORCID: https://orcid.org/0000-0001-5579-9487)
- Ethan Hill (ORCID: https://orcid.org/0009-0004-3816-1771)
- Chia-Yi Kuan
- Aden Weybright
Institutions
- St. Jude Children's Research Hospital (US)
- National Sun Yat-sen University (TW)
- University of Virginia Medical Center (US)
- University of Virginia (US)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1038/s41551-025-01362-3
- Citations
- 10
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 9.09
Funders
- St. Jude Children's Research Hospital
- American Lebanese Syrian Associated Charities
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering