In vivo visualization of α-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzoxazole positron emission tomography in multiple system atrophy

Akio Kikuchi, Atsushi Takeda, Nobuyuki Okamura, Manabu Tashiro, Takafumi Hasegawa, Shozo Furumoto, Michiko Kobayashi, Naoto Sugeno, Toru Baba, Yasuo Miki, Fumiaki Mori, Koichi Wakabayashi, Yoshihito Funaki, Ren Iwata, Shoki Takahashi, Hiroshi Fukuda, Hiroyuki Arai, Yukitsuka Kudo, Kazuhiko Yanai, Yasuto Itoyama

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91 Citations (Scopus)

Abstract

The histopathological hallmark of multiple system atrophy is the appearance of intracellular inclusion bodies, named glial cytoplasmic inclusions, which are mainly composed of α-synuclein fibrils. In vivo visualization of α-synuclein deposition should be used for the diagnosis and assessment of therapy and severity of pathological progression in multiple system atrophy. Because 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole could stain α-synuclein-containing glial cytoplasmic inclusions in post-mortem brains, we compared the carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography findings of eight multiple system atrophy cases to those of age-matched normal controls. The positron emission tomography data demonstrated high distribution volumes in the subcortical white matter (uncorrected P < 0.001), putamen and posterior cingulate cortex (uncorrected P < 0.005), globus pallidus, primary motor cortex and anterior cingulate cortex (uncorrected P < 0.01), and substantia nigra (uncorrected P < 0.05) in multiple system atrophy cases compared to the normal controls. They were coincident with glial cytoplasmic inclusion-rich brain areas in multiple system atrophy and thus, carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]- 6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography is a promising surrogate marker for monitoring intracellular α-synuclein deposition in living brains.

Original languageEnglish
Pages (from-to)1772-1778
Number of pages7
JournalBrain
Volume133
Issue number6
DOIs
Publication statusPublished - 2010 Jun

Keywords

  • Glial cytoplasmic inclusion
  • Lewy body
  • Parkinson's disease
  • Pittsburgh compound B
  • β-amyloid

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