New Radiotracers Outperform FDA-Approved Imaging Agent in Detecting Tau Tangles

Two new PET radiotracers have outperformed the only currently US FDA-approved radiotracer for detecting tau tangles in the brain, a hallmark of Alzheimer disease. In a head-to-head comparison of the three imaging agents, the next-generation radiotracers exhibited higher binding to Alzheimer disease brain tissue and a greater selectivity for identifying the tangles. This research, published in The Journal of Nuclear Medicine, could play a key role in measuring outcomes of clinical trials for Alzheimer disease treatments.

In Alzheimer disease, tau tangles are correlated with cognitive impairment: the more tangles, the more severe the impairment. By quantifying the amount of tau in the brain tissue with PET imaging, physicians can appropriately stage Alzheimer disease in patients and determine the best treatment options.

“Identifying tau tangles is crucial for diagnosing and staging Alzheimer disease,” said Pedro Rosa-Neto, MD, PhD, director of the Translational Neuroimaging Laboratory in the Douglas Research Centre at McGill University in Montreal, Quebec. “In our study we tested three different tau radiotracers to determine how well they could discriminate late-stage Alzheimer disease brain tissue from healthy brain tissue.”

In the study, autoradiography was used to assess the binding of¹⁸F-Flortaucipir (FDA- approved),¹⁸F-MK6240 and¹⁸F-PI2620 in autopsy-confirmed Alzheimer disease and healthy brain tissues. Binding values were calculated based on regions of interest in the prefrontal cortex, hippocampus, and cerebellar cortex sections of the brain, as well as the whole-brain hemisphere.

For all three radiotracers, a significant difference in binding was noted between the Alzheimer disease brain tissue and the healthy brain tissue in the whole brain hemisphere, prefrontal cortex, and hippocampus, but not the cerebellar cortex. Binding to Alzheimer disease brain tissue was higher for¹⁸F-MK6240 and¹⁸F-PI2620 than for¹⁸F-Flortaucipir.¹⁸F-MK6240 and¹⁸F-PI2620 also had greater selectivity than¹⁸F-Flortaucipir.

“With their higher specificity, these new tau imaging agents are ideal for detecting the small changes that occur in brain tissue over time,” noted Eduardo R. Zimmer, PhD, assistant professor of pharmacology at the Universidade Federal do Rio Grande do Sul, in Porto Alegre, Brazil. “This can be especially helpful in Alzheimer disease clinical trials that utilize tau PET as an outcome measure.”

Additionally, the study indicates that harmonization methods are needed to circumvent the differences between tau imaging agents. “Our work represents an important step toward the harmonization of tau tracers,” Zimmer said, “and the results might provide insights into initiatives to create a universal scale for tau tracers.”