Neuroimaging-pathological correlations of [18F]THK5351 PET in progressive supranuclear palsy

Aiko Ishiki, Ryuichi Harada, Hideaki Kai, Naomi Sato, Tomoko Totsune, Naoki Tomita, Shoichi Watanuki, Kotaro Hiraoka, Yoichi Ishikawa, Yoshihito Funaki, Ren Iwata, Shozo Furumoto, Manabu Tashiro, Hironobu Sasano, Tetsuyuki Kitamoto, Yukitsuka Kudo, Kazuhiko Yanai, Katsutoshi Furukawa, Nobuyuki Okamura, Hiroyuki Arai

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Recent positron emission tomography (PET) studies have demonstrated the accumulation of tau PET tracer in the affected region of progressive supranuclear palsy (PSP) cases. To confirm the binding target of radiotracer in PSP, we performed an imaging-pathology correlation study in two autopsy-confirmed PSP patients who underwent [18F]THK5351 PET before death. One patient with PSP Richardson syndrome showed elevated tracer retention in the globus pallidus and midbrain. In a patient with PSP-progressive nonfluent aphasia, [18F]THK5351 retention also was observed in the cortical areas, particularly the temporal cortex. Neuropathological examination confirmed PSP in both patients. Regional [18F]THK5351 standardized uptake value ratio (SUVR) in antemortem PET was significantly correlated with monoamine oxidase-B (MAO-B) level, reactive astrocytes density, and tau pathology at postmortem examination. In in vitro autoradiography, specific THK5351 binding was detected in the area of antemortem [18F]THK5351 retention, and binding was blocked completely by a reversible selective MAO-B inhibitor, lazabemide, in brain samples from these patients. In conclusion, [18F]THK5351 PET signals reflect MAO-B expressing reactive astrocytes, which may be associated with tau accumulation in PSP.

Original languageEnglish
Pages (from-to)53
Number of pages1
JournalActa Neuropathologica Communications
Volume6
Issue number1
DOIs
Publication statusPublished - 2018 Jun 29

Keywords

  • Monoamine oxidase
  • PET
  • PSP
  • Reactive astrocyte
  • Tau
  • [18F]THK5351

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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