@article{a6ed39b660454ba4bf0c46c5dd3f2f8e,
title = "In vivo binding of a tau imaging probe, [11C]PBB3, in patients with progressive supranuclear palsy",
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.",
keywords = "imaging, movement disorders, progressive supranuclear palsy, tau, tau imaging",
author = "Hironobu Endo and Hitoshi Shimada and Naruhiko Sahara and Maiko Ono and Shunsuke Koga and Soichiro Kitamura and Fumitoshi Niwa and Shigeki Hirano and Yasuyuki Kimura and Masanori Ichise and Hitoshi Shinotoh and Zhang, {Ming Rong} and Satoshi Kuwabara and Dickson, {Dennis W.} and Tatsushi Toda and Tetsuya Suhara and Makoto Higuchi",
note = "Funding Information: Funding agencies: This work was supported by grants from Grants-in-Aid for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS; 15653129) to T.S. and M.H., Research and Development Grants for Dementia (16768966) to M.H. from the Japan Agency for Medical Research and Development, the Japan Advanced Molecular Imaging Program and Grants-in-Aid for Young Scientists (A) (26713031) to H.S., and Scientific Research on Innovative Areas Funding Information: agencies: This work was supported by grants from Grants-in-Aid for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS; 15653129) to T.S. and M.H., Research and Development Grants for Dementia (16768966) to M.H. from the Japan Agency for Medical Research and Development, the Japan Advanced Molecular Imaging Program and Grants-in-Aid for Young Scientists (A) (26713031) to H.S., and Scientific Research on Innovative Areas (“Brain Environment” 23111009 to M.H. and “Brain Protein Aging” 26117001 to N.S.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and Mochida Memorial Foundation for Medical Pharmaceutical Research to H.S.The authors thank all subjects, their families, and volunteers for their participation in the study. We also thank the patients who donated brains. We also acknowledge the support of K. Takahata, S. Moriguchi, T. Sasaki, H. Fujiwara, F. Kodaka, S. Furukawa, Y. Eguchi, K. Yamaoka, A. Isato, M. Maruyama, H. Takano, I. Kaneko, K. Suzuki, J. Ichikawa, S. Kawakami, Y. Toyota, M. Kurokawa, A. Kurose, Y. Iwasawa, and the radiochemistry staffs and the radiological technologists at the NIRS (no particular order). We acknowledge the introduction of patients with PSP of Y. Yoshiyama at the Department of Neurology, Chiba-East National Hospital. We acknowledge the advice for statistical analysis by T. Shibata at the Center for Research Administration and Support, National Cancer Center. Publisher Copyright: {\textcopyright} 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.",
year = "2019",
month = may,
doi = "10.1002/mds.27643",
language = "English (US)",
volume = "34",
pages = "744--754",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "John Wiley and Sons Inc.",
number = "5",
}