New tau PET tracer outperforms standard agent in Alzheimer’s disease

A new PET radiotracer can detect tau pathology associated with Alzheimer’s disease before symptoms appear and more often than the method currently used in clinical practice, according to a study published May 28 in the Lancet. 

The findings are from a head-to-head comparison between F-18 MK-6240 and F-18 flortaucipir among 682 participants, with F-18 MK-6240 detecting tau pathology more than twice as often in cognitively unimpaired patients, noted corresponding author Tharick Pascoal, MD, PhD, of the University of Pittsburgh, and colleagues. 

“Tau is the biology most closely tied to symptoms and future decline,” Pascoal said, in a news release from the university. “If we can detect tau earlier and stage it more precisely, we can make better decisions about who is truly on an Alzheimer’s trajectory, which matters for clinical trials now and could shape clinical decision-making as new therapies emerge.” 

Along with amyloid-plaque deposits, tau tangles are a hallmark of Alzheimer’s disease. Current theories (the “cascade hypothesis”) suggest that beta amyloid is the initial trigger of pathological tau and precedes symptom onset by decades, while tau is the actual driver of neurodegeneration and cognitive decline. 

To date, more than 95% of sites in the U.S. perform tau PET studies using F-18 MK-6240 or F-18 flortaucipir (Tauvid, Eli Lilly), Pascoal and colleagues noted. Although both tracers offer robust tau estimates, large differences in binding characteristics between them can lead to misleading interpretations of their outcomes. Differences also preclude the merging of their datasets using simple conversion methods, the researchers added. 

To further elucidate their advantages and limitations for research, trials, and practice, the researchers recruited 682 participants from eight U.S. sites between March 2022 and August 2025. The cohort included 373 (55%) women 309 (45%) men, with 38 (6%) ages 19 to 27 years old (control subjects), 214 (31%) ages 50 to 65 years old, and 430 (63%) ages 65 to 89 years old. 

All participants underwent paired tau PET scans with both F-18 flortaucipir and F-18 MK-6240, as well as an amyloid PET scan and detailed cognitive assessments, all within a 45-day window. 

According to the results, F-18 MK6240 detected tau positivity more often than F-18 flortaucipir. In cognitively unimpaired, amyloid-β-positive participants, MK6240 identified more than twice as many tau-positive cases as flortaucipir (15% versus 6%), corresponding to 23 additional cases per 100. Among cognitively-impaired participants, F-18 MK6240 also identified more tau involvement than F-18 flortaucipir (28% versus 16%), corresponding to 15 additional mild cognitive-impairment cases and 21 additional dementia cases per 100 people scanned.

PET brain scans from the same individual with early signs of Alzheimer’s disease comparing two tau radiotracers: flortaucipir, shown at top, and the investigational tracer MK6240, shown at bottom. Areas of pathological tau accumulation appear in red. The MK6240 scan shows more extensive tau buildup, suggesting that this tracer may detect Alzheimer’s-related brain changes that are less visible with the standard tracer.Pascoal lab, University of Pittsburgh“Tau PET tracer selection influences the frequency of detection of tau pathology across the aging and Alzheimer’s disease spectrum,” the researchers wrote. 

The group noted that F-18 MK-6240's performance advantage reflects its approximately sixfold greater affinity for tau tangles. While F-18 flortaucipir is approved for detecting advanced tau pathology, F-18 MK-6240 is pending approval at the U.S. Food and Drug Administration (FDA), they added. 

“Earlier detection might refine Alzheimer’s disease staging and enhance the selection of individuals for therapeutic intervention in both clinical trials and routine practice,” the researchers concluded. 

The full study is available here.