PET tracer derived from an ALS treatment provides a method to quantify damage from oxidative stress in the brain.
A newly developed positron emission tomography (PET) imaging probe, derived from the drug edaravone, has demonstrated potential for detecting oxidative stress in the central nervous system – an underlying factor in neurodegenerative diseases such as Alzheimer’s and amyotrophic lateral sclerosis (ALS).
Researchers at St Jude Children’s Research Hospital and the University of Virginia have developed [18F]fluoroedaravone ([18F]FEDV), a radio-labeled analogue of the antioxidant edaravone, which enables in vivo imaging of reactive oxygen and nitrogen species (RONS) in the brain. The study, published in Nature Biomedical Engineering, highlights the importance of this development in understanding the role of oxidative stress in neurodegeneration.
Longevity.Technology: This study addresses a longstanding challenge: the inability to directly measure reactive oxygen and nitrogen species (RONS) in vivo in the central nervous system. The development of [18F]FEDV, a PET tracer derived from edaravone, offers a powerful tool for visualizing oxidative stress at a cellular level – something that has been a critical gap in evaluating the efficacy of antioxidant therapies for neurodegenerative diseases. By successfully crossing the blood-brain barrier and demonstrating stability in human plasma, [18F]FEDV enables real-time, longitudinal tracking of RONS activity, making it highly relevant for assessing disease progression and therapeutic interventions in conditions like Alzheimer’s disease and stroke. The broad reactivity of [18F]FEDV with lipid- and water-soluble peroxyl radicals further speaks to its versatility as an oxidative stress biomarker.
If translated to clinical use, this imaging tool could refine patient selection for antioxidant-based interventions, monitor treatment responses with unprecedented precision and even predict symptom onset, offering the potential to reshape how oxidative stress is understood and targeted in aging and neurodegenerative disease management.
Oxidative stress as a driver of neurodegeneration
Reactive oxygen and nitrogen species contribute to cellular signaling and homeostasis; however, when their production exceeds the capacity of the body’s antioxidant systems, they initiate damaging chain reactions. Excessive RONS activity has been implicated in neuronal injury, mitochondrial dysfunction and the pathological progression of neurodegenerative diseases, but despite this, direct measurement of oxidative stress in the living brain has remained a challenge.
A novel PET imaging approach
Edaravone, originally approved for ALS treatment, scavenges peroxyl radicals, hydroxyl radicals and peroxynitrite – compounds that contribute to oxidative injury. [18F]FEDV retains these properties while being radio-labeled for PET imaging, allowing it to serve as a biomarker for oxidative stress. Unlike other PET tracers that detect neuroinflammation or amyloid deposition, [18F]FEDV provides a direct measure of oxidative stress levels, enabling longitudinal monitoring of disease progression and response to antioxidant treatments.
The study demonstrated that [18F]FEDV can cross the blood–brain barrier and selectively accumulate in regions with high oxidative stress. In mouse models, the tracer detected RONS accumulation following induced stroke and in brains with tauopathy, a characteristic of Alzheimer’s disease. Its specificity was confirmed by pre-treating mice with edaravone, which blocked the PET signal, indicating that the probe directly measures oxidative stress rather than other metabolic processes [1].
“It’s the subsequent secondary injury, which usually comes from the immune response, which causes the most neurological damage,” explained corresponding author Kiel Neumann, PhD, St Jude Department of Radiology. “Part of that immune response is a burst of reactive oxygen and nitrogen species, sometimes called an oxidative burst [2].”
Implications for clinical research and diagnosis
The ability to visualize oxidative stress in real time could significantly enhance the study of neurodegeneration. As clinical trials of antioxidants have produced mixed results, partly due to the lack of a method to confirm their effect in vivo, [18F]FEDV could serve as a crucial tool for evaluating therapeutic efficacy. By enabling direct measurement of oxidative stress, the tracer may also assist in identifying individuals at risk of developing neurodegenerative conditions before symptoms emerge.
“The goal in imaging is to promote contrast, so we want something that engages with its target rapidly but then also rapidly clears so you can see your target right away,” explained Neumann. “What was unique about this drug is that when it reacts with oxidative stress, it undergoes a massive structural and polarity change which keeps it in the cell and promotes contrast [2].”
Next steps
Further research will be needed to validate [18F]FEDV in human studies. The next steps include clinical trials to assess its safety and efficacy in patients with ALS, Alzheimer’s disease and other neurodegenerative conditions. Additionally, researchers aim to refine PET imaging protocols to enhance the sensitivity and resolution of oxidative stress detection in the human brain.
“Our diagnostic tests are on the order of nanograms to micrograms of material, so the body doesn’t even know it’s there,” Neumann said. “Ultimately, our goal is to use this to impact clinical care. Therapeutic intervention using this technology for clinical disease management is the future [2].”
With its potential to fill a longstanding gap in neurodegenerative research, [18F]FEDV represents an advance in molecular imaging – one that could lead to earlier and more precise diagnosis of conditions linked to oxidative stress, as well as improved strategies for their treatment.
[1] https://www.nature.com/articles/s41551-025-01362-3
[2] https://www.stjude.org/media-resources/news-releases/2025-medicine-science-news/repurposed-als-drug-becomes-imaging-probe-to-help-diagnose-neurodegeneration.html
