A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system
Year: 2025
Type: article
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. A positron emission tomography tracer of reactive oxygen and nitrogen species enables the in vivo quantification of oxidative stress, as shown in mouse models of oxidative stress, stroke and tauopathy.
Source: Nature Biomedical Engineering
Authors: 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
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: U.S. Department of Health and Human Services, St. Jude Children's Research Hospital, American Lebanese Syrian Associated Charities, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Novel imaging agents of oxidative stress in the pathophysiology of the central nervous system, G1090891292, G2179486046, G4402345302, Perivascular Fibroblast-Endothelium Interactions in Hypertension and Cerebral Ischemia, CMRO2 and Uncoupling of Oxidative-Phosphorylation in Experimental HIE, G5325608099, G6067391662, G6086668728, G654514939, G6611928351, Monocyte-Derived Microglia in Development and after Neonatal Brain Injury, G7661642065, Neutrophils and Monocytes in Pediatric Ischemic Stroke, G8468171315, G9000120510, G9000179414, G9000199720, G9000211255, G9000347428, G9000351132, Treating neurotoxicity and cognitive deficits due to hyperphosphorylated tau., G973717862
OpenAlex ID: W4408161036