In vivo binding of a tau imaging probe, [11 C]PBB3, in patients with progressive supranuclear palsy

Mov Disord. 2019 May;34(5):744-754. doi: 10.1002/mds.27643. Epub 2019 Mar 20.

Abstract

Background: [11 C]pyridinyl-butadienyl-benzothiazole 3 is a PET imaging agent designed for capturing pathological tau aggregates in diverse neurodegenerative disorders, and would be of clinical utility for neuropathological investigations of PSP.

Objectives: To explore the usefulness of [11 C]pyridinyl-butadienyl-benzothiazole 3/PET in assessing characteristic distributions of tau pathologies and their association with clinical symptoms in the brains of living PSP patients.

Methods: We assessed 13 PSP patients and 13 age-matched healthy control subjects. Individuals negative for amyloid β PET with [11 C]Pittsburgh compound B underwent clinical scoring, MR scans, and [11 C]pyridinyl-butadienyl-benzothiazole 3/PET.

Results: There were significant differences in binding potential for [11 C]pyridinyl-butadienyl-benzothiazole 3 between PSP patients and healthy control subjects (P = 0.02). PSP patients exhibited greater radioligand retention than healthy control subjects in multiple brain regions, including frontoparietal white matter, parietal gray matter, globus pallidus, STN, red nucleus, and cerebellar dentate nucleus. [11 C]pyridinyl-butadienyl-benzothiazole 3 deposition in frontoparietal white matter, but not gray matter, was correlated with general severity of parkinsonian and PSP symptoms, whereas both gray matter and white matter [11 C]pyridinyl-butadienyl-benzothiazole 3 accumulations in the frontoparietal cortices were associated with nonverbal cognitive impairments. Autoradiographic and fluorescence labeling with pyridinyl-butadienyl-benzothiazole 3 was observed in gray matter and white matter of PSP motor cortex tissues.

Conclusions: Our findings support the in vivo detectability of tau fibrils characteristic of PSP by [11 C]pyridinyl-butadienyl-benzothiazole 3/PET, and imply distinct and synergistic contributions of gray matter and white matte tau pathologies to clinical symptoms. [11 C]pyridinyl-butadienyl-benzothiazole 3/PET potentially provides a neuroimaging-based index for the evolution of PSP tau pathologies promoting the deterioration of motor and cognitive functions. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Keywords: imaging; movement disorders; progressive supranuclear palsy; tau; tau imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aniline Compounds
  • Autoradiography
  • Benzothiazoles
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Carbon Radioisotopes
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Supranuclear Palsy, Progressive / diagnostic imaging*
  • Thiazoles
  • tau Proteins / metabolism*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Benzothiazoles
  • Carbon Radioisotopes
  • Carbon-11
  • PBB3 compound
  • Thiazoles
  • tau Proteins