Colleagues at Siemens Healthcare's Molecular Imaging team recently published research data on a compound that selectively targets neurofibrillary tangles (NFTs) of tau protein, one of two prominent hallmark of Alzheimer’s disease. The [18F]-T808 compound is used in positron emission tomography (PET) imaging and is being developed as a potential agent for commercialization. The data appeared in the study “A Highly Selective and Specific PET Tracer for Imaging Tau Pathologies” and was published in the August 2012 issue of the Journal of Alzheimer’s Disease.
Tau as Alzheimer’s hallmark
NFTs of hyperphosphorylated tau protein are one of two critical protein abnormalities, Amyloid and Tau, associated with Alzheimer’s disease and are considered to be target for therapeutic intervention, in addition to being imaging biomarker 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, in addition to the recently released and in clinical use Amyloid imaging biomarker.
Research on the compound
A research team led by Hartmuth C. Kolb, PhD, vice president of Molecular Imaging Biomarker Research at Siemens Healthcare, designed, synthesized, and tested 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. The compound demonstrated rapid uptake and washout in rodent brains. The researchers’ in vivo and in vitro studies suggest that [18F]-T808 possesses suitable properties and characteristics to be a specific and selective Tau PET tracer for the imaging of paired helical filament tau in human brains.[18F]-T808 is the first highly selective and specific PET tracer with potential for in vivo neurological imaging of tau pathologies.
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