Next-Generation Tau Radiotracers Outperform FDA-Approved Imaging Agents in Detecting Alzheimer’s Disease

Reston, VA (January 28, 2025)—Two new PET radiotracers have outperformed the only currently Food and Drug Administration (FDA) approved radiotracer for detecting tau tangles in the brain, a hallmark of Alzheimer’s disease. In a head-to-head comparison of the three imaging agents, the next-generation radiotracers exhibited higher binding to Alzheimer’s disease brain tissue and a greater selectivity for identifying the tangles. This research, which was published in the January issue of The Journal of Nuclear Medicine, could play a key role in measuring outcomes of clinical trials for Alzheimer’s disease treatments.

In Alzheimer’s 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’s disease in patients and determine the best treatment options.

“Identifying tau tangles is crucial for diagnosing and staging Alzheimer’s 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’s disease brain tissue from healthy brain tissue.”

In the study, autoradiography was used to assess the binding of ¹⁸F-Flortaucipir (FDA-approved), ¹⁸F-MK6240 and ¹⁸F-PI2620 in autopsy-confirmed Alzheimer’s 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’s 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’s disease brain tissue was higher for ¹⁸F-MK6240 and ¹⁸F-PI2620 than for ¹⁸F-Flortaucipir. ¹⁸F-MK6240 and ¹⁸F-PI2620 also had greater selectivity than ¹⁸F-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’s 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.”

Figure 1. Autoradiography images showing binding of [¹⁸F]flortaucipir, [¹⁸F]MK6240, and [¹⁸F]PI2620 in prefrontal cortex, hippocampus, and cerebellum (A) and in whole-brain hemisphere (B) of control and AD brains. CN = control.

The authors of “Comparison Between Brain and Cerebellar Autoradiography Using [¹⁸F]Flortaucipir, [¹⁸F]MK6240, and [¹⁸F]PI2620 in Postmortem Human Brain Tissue” include Antonio Aliaga, Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Quebec, Canada, Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and Research Institute of McGill University Health Centre, Montreal, Quebec, Canada; Joseph Therriault, Nesrine Rahmouni, Arthur C. Macedo, and Peter Kunach, Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Quebec, Canada, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada, and Montreal Neurological Institute, Montreal, Quebec, Canada; Kely Monica Quispialaya, Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Quebec, Canada, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada, Montreal Neurological Institute, Montreal, Quebec, Canada, and Department of Medicine, McGill University, Montreal, Quebec, Canada; Arturo Aliaga, Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Quebec, Canada, and Montreal Neurological Institute, Montreal, Quebec, Canada; Robert Hopewell, Jean-Paul Soucy, Gassan Massarweh, and Marie-Christine Guiot, Montreal Neurological Institute, Montreal, Quebec, Canada; Aida Abreu Diaz, Department of Pharmacology and Physiology, University of Montreal, Montreal, Quebec, Canada; Tharick A. Pascoal, Department of Psychiatry, Pittsburgh University, Pittsburgh, Pennsylvania; Andreia Rocha, Luiza S. Machado, Marco Antônio De Bastiani, Débora Guerini de Souza, and Diogo O. Souza, Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Serge Gauthier, Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Quebec, Canada, and Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Eduardo R. Zimmer, Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Quebec, Canada, Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; and Pedro Rosa-Neto, Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montreal, Quebec, Canada, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada, and Montreal Neurological Institute, Montreal, Quebec, Canada.

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