Study touts [18F]-T808 as first selective PET tracer for tau protein pathologies

Twitter icon
Facebook icon
LinkedIn icon
e-mail icon
Google icon
elderly woman - 42.09 Kb

Research on the first highly selective and specific PET tracer for in vivo neurological imaging of tau pathologies has been published in the August issue of Journal of Alzheimer’s Disease.

In the article, Hartmuth C. Kolb, PhD, vice president of Molecular Imaging Biomarker Research at Siemens Healthcare, and colleagues demonstrated selective binding of [18F]-T808 to tau tangles with in vitro autoradiographic assays using sections of human brain tissue. They also noted high levels of binding affinity, selectivity and specificity during preclinical characterization, which “makes [[18F]-T808] a suitable candidate as a PET tracer for tau aggregate imaging.”

Kolb and colleagues tested more than 900 compounds using a competitive autoradiography assay in more than 40 brains to test compounds for binding to native tau tangles and amyloid-beta plaques. Early in the process of analyzing tau and amyloid-beta burden, one compound was shown to have selective binding to tau over amyloid-beta deposits, and this compound was then tested against several hundred others.

“This screening process yielded a highly selective tracer, [18F]-T808, that shows no binding to amyloid-beta deposits,” wrote the authors. “In addition, our studies show that there is remarkably low background binding in normal brains and almost no white matter binding, which will contribute greatly to the sensitivity of this tracer.”

In vivo, the compound demonstrated rapid uptake and washout in rodent brains, with [18F]-T808 clearing from the brain in less than 15 minutes.

“While there are a number of amyloid-beta [PET] tracers currently in different stages of clinical development and commercialization, there have been very few reports on imaging agents selectively targeting tau aggregates,” wrote Kolb et al. They explained that neurofibrillary tangles composed of paired helical filaments of tau protein are also a critical protein abnormality associated with Alzheimer’s disease.

“Until reliable imaging methods are developed to detect neurofibrillary changes, it is impossible to follow the same individual over long periods of time and measure changes in the brain,” wrote the authors. “Noninvasive methods to detect these abnormal proteins are therefore highly desirable in developing surrogate biomarkers for early and accurate diagnosis of the disease.”

Kolb and colleagues plan to test [18F]-T808 clinically in Alzheimer’s disease patients to assess its usefulness as an early diagnostic tool.