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

Hironobu Endo, Hitoshi Shimada, Naruhiko Sahara, Maiko Ono, Shunsuke Koga, Soichiro Kitamura, Fumitoshi Niwa, Shigeki Hirano, Yasuyuki Kimura, Masanori Ichise, Hitoshi Shinotoh, Ming Rong Zhang, Satoshi Kuwabara, Dennis W. Dickson, Tatsushi Toda, Tetsuya Suhara, Makoto Higuchi

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: [11C]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 [11C]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 [11C]Pittsburgh compound B underwent clinical scoring, MR scans, and [11C]pyridinyl-butadienyl-benzothiazole 3/PET. Results: There were significant differences in binding potential for [11C]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. [11C]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 [11C]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 [11C]pyridinyl-butadienyl-benzothiazole 3/PET, and imply distinct and synergistic contributions of gray matter and white matte tau pathologies to clinical symptoms. [11C]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.

Original languageEnglish (US)
Pages (from-to)744-754
Number of pages11
JournalMovement Disorders
Volume34
Issue number5
DOIs
StatePublished - May 2019

Keywords

  • imaging
  • movement disorders
  • progressive supranuclear palsy
  • tau
  • tau imaging

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Endo, H., Shimada, H., Sahara, N., Ono, M., Koga, S., Kitamura, S., Niwa, F., Hirano, S., Kimura, Y., Ichise, M., Shinotoh, H., Zhang, M. R., Kuwabara, S., Dickson, D. W., Toda, T., Suhara, T., & Higuchi, M. (2019). In vivo binding of a tau imaging probe, [11C]PBB3, in patients with progressive supranuclear palsy. Movement Disorders, 34(5), 744-754. https://doi.org/10.1002/mds.27643