PET Imaging Agent for Detection of Tau Pathologies Shows Promise for Alzheimer’s Patients

Siemens Healthcare, which supported the study research in its entirety, is developing the [18F]-labeled compound as a potential PET imaging agent for commercialization. The study’s findings were published in the August 2012 issue of the Journal of Alzheimer’s Disease.

NFTs of hyperphosphorylated tau protein are one of two critical protein abnormalities associated with AD, the other being senile plaques consisting of beta-amyloid peptides. Both protein abnormalities are considered to be targets for therapeutic intervention, in addition to being biomarkers for diagnostic in vivo imaging agents. The severity of tau abnormalities and NFT burden consistently correlates with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimer’s disease dementia, whereas the presence of senile brain plaques lack that correlation. For this reason, NFT can potentially be an additional imaging biomarker for Alzheimer’s-related dementia.

A research team led by Hartmuth C. Kolb, PhD, vice president of molecular imaging biomarker research at Siemens Healthcare, designed, synthesized, and assessed more than 900 compounds in an effort to identify [18F]-PET tracers that possess strong binding affinity and selectivity toward tau protein tangles. Researchers created a competitive autoradiography assay to test compounds that would bind to native tau tangles and beta-amyloid plaques on sections of postmortem human brain tissue.

In in-vitro assays, the compound [18F]-T808 displayed a high level of binding affinity and good selectivity for tau aggregates over beta-amyloid plaques. The compound showed quick uptake and washout in rat brains. The researchers’ in vivo and in vitro studies suggest that [18F]-T808 possesses suitable characteristics to be a specific and selective PET tracer for the imaging of paired helical filament tau in human brains.

“Highly selective and high-affinity tau PET imaging agents are needed to support evaluation and research into potential therapeutic efforts to manage tau-related diseases,” Dr. Kolb said. “Preclinical characterization of [18F]-T808 demonstrated high levels of binding affinity, selectivity, and specificity, which makes this agent a suitable candidate for further study as a PET tracer for tau aggregate imaging.”

A major issue with AD is identifying a biomarker that can be correlated with the progression of clinical symptoms and allow extrapolation back to early preclinical stages. This appears possible in the case of tau deposits. The study’s authors plan to assess the [18F]-T808 tracer clinically in Alzheimer’s disease patients to determine its usefulness as an early diagnostic tool of the disease.

[18F]-T808 is the first highly selective and specific PET tracer with potential for in vivo neurological imaging of tau pathologies. It is metabolically stable and has fast uptake and rapid washout period in rodents.

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