PET Imaging and Blood Biomarker Studies Advance Toward First In-Life Diagnosis of Chronic Traumatic Encephalopathy
Key Insights
A first-in-class PET radiotracer, 18F-OXD-2314 (search), demonstrated elevated uptake in grey-white matter junctions of retired athletes with suspected CTE compared to healthy controls.
The tracer also showed binding in all post-mortem CTE tissue examined, providing early biological confirmation of its ability to detect tau (search) pathology specific to CTE.
Separately, the Alzheimer's-associated protein eMTBR-tau243 (search) showed stage-specific increases in blood samples from donors with confirmed CTE pathology, rising from Stage I to Stage IV disease.
Two independent lines of research presented at major scientific meetings are converging on a long-elusive goal in neurodegenerative disease: diagnosing chronic traumatic encephalopathy (search) (CTE) in living patients. Currently, CTE—a devastating tauopathy linked to repeated head impacts—can only be definitively confirmed through post-mortem neuropathological examination. Now, a novel PET imaging tracer and a blood-based protein assay are each showing early promise in detecting the disease before death.
A First-in-Class PET Tracer for CTE
At the Society of Nuclear Medicine and Molecular Imaging 2026 Annual Meeting, researchers presented findings on 18F-OXD-2314 (search), a new tau (search) PET radiotracer designed to recognize the distinct tau pathology seen in CTE. The study, led by Isabelle Boileau, PhD, senior scientist and associate director of the Brain Health Imaging Centre at the Centre for Addiction and Mental Health in Toronto, evaluated the tracer in three retired collision-sport athletes with suspected CTE and seven healthy controls.
Dynamic brain PET imaging revealed elevated uptake of 18F-OXD-2314 (search) in the grey-white matter junction and in white matter of individuals with suspected CTE compared to healthy controls. Critically, additional autoradiography studies using 3H-OXD-2314 demonstrated binding in all post-mortem CTE cases examined, providing early biological confirmation that the tracer binds to tau (search) pathology in human CTE tissue.
"Post-mortem, CTE is confirmed by the presence of tau (search) plaques in the brain," said Boileau. "Existing tau PET tracers, however, are largely developed for Alzheimer's disease and may not adequately detect the distinct tau pathology seen in CTE."
Boileau emphasized the potential clinical impact: "If validated, 18F-OXD-2314 (search) could help provide the first accurate in-life diagnostic biomarker for CTE. This work could also establish a clinical role for PET in traumatic brain injury and sports- and military-related neurodegeneration and spark next generation tau (search)-radiopharmaceuticals optimized for non-Alzheimer's disease tauopathies including CTE."
While still in early clinical research, the data in both people with suspected CTE and other non-Alzheimer's disease tauopathies are "very promising," Boileau noted, adding that PET imaging for CTE could be available to patients as early as the next two years, pending further studies.
A Blood Biomarker from Alzheimer's Research
In a separate but complementary development, researchers at Washington University in St. Louis reported that eMTBR-tau243 (search)—a protein marker originally developed for Alzheimer's disease—may also help diagnose CTE in living individuals. The findings were presented July 15 at the Alzheimer's Association International Conference in London and have yet to be peer-reviewed.
Neuroscientist Chihiro Sato and colleague Kanta Horie, who is employed by Eisai Inc. while working at Washington University, were initially studying eMTBR-tau243 (search) as a diagnostic for Alzheimer's disease. The team had shown that across 112 patients with eight different brain diseases, only those with Alzheimer's—or Alzheimer's alongside another condition—showed elevated levels of the protein. But one "very surprising" outlier emerged: a patient with advanced CTE.
Recognizing that tau (search) protein clumps in Alzheimer's and CTE likely share similar structural characteristics, the team collaborated with researchers at the University of California, San Francisco to acquire blood and cerebrospinal fluid samples from brain donors. This included 11 blood samples from individuals whose brains had confirmed CTE pathology.
In these donors, the eMTBR-tau243 (search) signal increased in a stage-specific manner. Donors with mild, Stage I CTE had eMTBR-tau243 levels significantly lower than those with advanced Stage IV disease. All levels were higher than in healthy brains. The team was able to acquire only two brains with moderate Stage III disease, but Sato said the team observed a trend suggesting their levels would sit between Stages I and IV.
"We think there's potential," Sato said, while acknowledging the results would need confirmation in a larger dataset.
The Urgency of In-Life Diagnosis
CTE is common among contact sports athletes, military veterans, victims of interpersonal or intimate partner violence, and anyone who has experienced traumatic brain injury. Individuals with suspected CTE often experience cognitive decline, mood symptoms, impulsivity, and dementia. A 2018 study found that CTE-like damage affected 1 of 164 donated brains, but the condition is far more prevalent in populations repeatedly exposed to head trauma. In 2023, the Boston University CTE Center reported that CTE pathology was present in more than 90 percent of brains in a sample of 376 former NFL players.
The ability to diagnose patients while alive would provide clarity to patients about their well-being and be invaluable to getting them involved in future trials of any CTE treatments, said John Arena, a neurosurgeon at the University of Pennsylvania who was not involved in the research.
Progress toward in-life diagnosis has not been straightforward. In 2019, an expert panel developed a clinical symptom checklist for identifying likely CTE, but Arena and colleagues showed in May that there was little correlation between patients who scored highly on the checklist and who later tested positive for CTE after death. "We really need to develop validated biomarkers to supplement that clinical picture," Arena said. "That's going to be critically important."
The two emerging approaches—PET imaging with 18F-OXD-2314 (search) and blood-based measurement of eMTBR-tau243 (search)—represent parallel paths toward that goal, each offering distinct advantages in the pursuit of the first validated in-life diagnostic for CTE.