Innovative PET Imaging Technique to Help Diagnose Neurodegeneration

Neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease, are often diagnosed only after physical symptoms appear, by which time treatment may no longer be effective. Positron emission tomography (PET) is a nuclear imaging method primarily used for diagnosing conditions like cancer. Now, an innovative advancement is enhancing the technique’s ability to detect signs of neurological diseases.

Researchers at St. Jude Children’s Research Hospital (Memphis, TN, USA) have repurposed the antioxidant drug edaravone, which is typically used to treat ALS, as a probe for central nervous system PET imaging. This innovative technique allows the detection of oxidative stress, a condition that contributes to brain damage, thus providing a clearer path for diagnosing neurological diseases. Reactive oxygen and nitrogen species (RONS) are a group of chemically reactive molecules crucial in cell signaling and growth. However, when RONS accumulate, they cause oxidative stress, leading to tissue damage and dysfunction. This stress is linked to various neurodegenerative diseases. Detecting oxidative stress through non-invasive imaging offers the potential to diagnose and treat conditions like ALS and Alzheimer’s disease earlier, when treatments could be more effective.

Apart from neurodegenerative conditions, oxidative stress also plays a role in numerous other neurological diseases, such as stroke. In these cases, damage does not solely occur from the initial injury. Reactive chemicals released during oxidative bursts, including hydroxyl and peroxyl radicals, can trigger a chain reaction of further oxidative damage. As an antioxidant, edaravone naturally interacts with RONS, prompting the researchers to propose that the drug could be used to enhance imaging efforts. To test this, they radiolabeled edaravone by replacing atoms in the molecule with radioactive isotopes, allowing them to track the movement and breakdown of the drug. Once administered, the radiolabeled drug emits positrons—subatomic particles detectable only by a PET scan—illuminating the area where the drug accumulates, which coincides with the buildup of RONS. The drug's ability to bind RONS even at low doses makes it ideal for PET imaging while still serving as an antioxidant treatment at standard doses, providing a dual benefit of diagnosis and therapy. These findings were published in Nature Biomedical Engineering.

“Our diagnostic tests are on the order of nanograms to micrograms of material, so the body doesn’t even know it’s there,” said corresponding author Kiel Neumann, PhD, St. Jude Department of Radiology. “Ultimately, our goal is to use this to impact clinical care. Therapeutic intervention using this technology for clinical disease management is the future.”