A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system

Justin H. Wilde; Yu Yo Sun; Spenser R. Simpson; Ethan R. Hill; Zhongxiao Fu; Emily J. Bian; Melissa M. Kinkaid; Paulina Villanueva; Aden F. Weybright; William R. Terrell; Zoraiz Qureshi; Shashika S. Perera; Heather S. Sheppard; James R. Stone; Bijoy K. Kundu; Chia Yi Kuan; Kiel D. Neumann

doi:10.1038/s41551-025-01362-3

A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system

Justin H. Wilde, Yu Yo Sun, Spenser R. Simpson, Ethan R. Hill, Zhongxiao Fu, Emily J. Bian, Melissa M. Kinkaid, Paulina Villanueva, Aden F. Weybright, William R. Terrell, Zoraiz Qureshi, Shashika S. Perera, Heather S. Sheppard, James R. Stone, Bijoy K. Kundu, Chia Yi Kuan, Kiel D. Neumann^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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, [¹⁸F]fluoroedaravone ([¹⁸F]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 [¹⁸F]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 [¹⁸F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [¹⁸F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants.

Original language	English
Article number	e98807
Journal	Nature Biomedical Engineering
DOIs	https://doi.org/10.1038/s41551-025-01362-3
State	Accepted/In press - 2025
Externally published	Yes

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10.1038/s41551-025-01362-3

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Wilde, J. H., Sun, Y. Y., Simpson, S. R., Hill, E. R., Fu, Z., Bian, E. J., Kinkaid, M. M., Villanueva, P., Weybright, A. F., Terrell, W. R., Qureshi, Z., Perera, S. S., Sheppard, H. S., Stone, J. R., Kundu, B. K., Kuan, C. Y., & Neumann, K. D. (Accepted/In press). A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system. Nature Biomedical Engineering, Article e98807. https://doi.org/10.1038/s41551-025-01362-3

@article{146a1a77866944a2ba598005b321b976,

title = "A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system",

abstract = "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, [18F]fluoroedaravone ([18F]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 [18F]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 [18F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [18F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants.",

author = "Wilde, {Justin H.} and Sun, {Yu Yo} and Simpson, {Spenser R.} and Hill, {Ethan R.} and Zhongxiao Fu and Bian, {Emily J.} and Kinkaid, {Melissa M.} and Paulina Villanueva and Weybright, {Aden F.} and Terrell, {William R.} and Zoraiz Qureshi and Perera, {Shashika S.} and Sheppard, {Heather S.} and Stone, {James R.} and Kundu, {Bijoy K.} and Kuan, {Chia Yi} and Neumann, {Kiel D.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

doi = "10.1038/s41551-025-01362-3",

language = "English",

journal = "Nature Biomedical Engineering",

issn = "2157-846X",

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Wilde, JH, Sun, YY, Simpson, SR, Hill, ER, Fu, Z, Bian, EJ, Kinkaid, MM, Villanueva, P, Weybright, AF, Terrell, WR, Qureshi, Z, Perera, SS, Sheppard, HS, Stone, JR, Kundu, BK, Kuan, CY & Neumann, KD 2025, 'A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system', Nature Biomedical Engineering. https://doi.org/10.1038/s41551-025-01362-3

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T1 - A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system

AU - Wilde, Justin H.

AU - Sun, Yu Yo

AU - Simpson, Spenser R.

AU - Hill, Ethan R.

AU - Fu, Zhongxiao

AU - Bian, Emily J.

AU - Kinkaid, Melissa M.

AU - Villanueva, Paulina

AU - Weybright, Aden F.

AU - Terrell, William R.

AU - Qureshi, Zoraiz

AU - Perera, Shashika S.

AU - Sheppard, Heather S.

AU - Stone, James R.

AU - Kundu, Bijoy K.

AU - Kuan, Chia Yi

AU - Neumann, Kiel D.

PY - 2025

Y1 - 2025

N2 - 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, [18F]fluoroedaravone ([18F]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 [18F]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 [18F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [18F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants.

AB - 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, [18F]fluoroedaravone ([18F]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 [18F]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 [18F]FEDV-PET to RONS allowed for the detection of increased oxidative stress. [18F]FEDV-PET could be used to quantify RONS longitudinally in vivo and to assess the results of clinical studies of antioxidants.

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