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

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.