Compound Stains Alpha-synuclein In Vivo

Subject: Compound Stains Alpha-synuclein In Vivo

Date: 6/14/2010

A novel imaging compound stains alpha-synuclein deposits in vivo in patients with multiple system atrophy, according to a new study.

The compound is a PET probe known as 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole, or BF-227. The authors labeled brain with BF-227 in both post-mortem brain and living subjects.

In post-mortem brain, they showed that fluorescent BF-227 colocalized with antibodies for alpha-synuclein in Lewy bodies in the substantia nigra of patients with Parkinson’s disease, in cortical Lewy bodies in patients with Lewy body dementia, and in glial cytoplasmic inclusions in patients with MSA.

In living subjects, they administered intravenous C-11 labeled BF-227 to 8 patients with MSA (4 MSA-C and 4 MSA-P) and 8 controls, followed by PET imaging for up to 60 minutes. Compared to controls, MSA patients had higher concentrations of BF-227 in subcortical white matter and lenticular nucleus, corresponding to regions of high Lewy body deposits in the post-mortem brains. Higher concentrations were also found in the putamen, posterior cingulate cortex, globus pallidus, primary motor cortex, and substantia nigra. “No obvious differences were found in either the distribution or degree of binding between the MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia subgroups,” they report.

“As shown in the present study, BF-227 is a promising tracer to detect glial cytoplasmic inclusions. Further studies are warranted to verify whether Lewy bodies in other alpha-synucleinopathies as well as glial cytoplasmic inclusions can be detected by [11C]-BF-227 PET,” the authors conclude. “These results suggest that [11C]-BF-227 PET is a suitable surrogate maker for monitoring alpha-synuclein deposits in living brains with MSA and could be a potential tool to monitor the effectiveness of neuroprotective therapy for alpha-synucleinopathies.”

They note that BF-227 is more lipophilic that Pittsburgh-B, a marker for Alzheimer’s pathology that has also been investigated for its ability to tag alpha-synuclein, with variable results.

In vivo visualization of alpha-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
A Kikuchi, A Takeda, N Okamura, M Tashiro, T Hasegawa, S Furumoto, M Kobayashi, N Sugeno, T Baba, Y Miki, F Mori, K Wakabayashi, Y Funaki, R Iwata, S Takahashi,
H Fukuda, H Arai, Y Kudo, K Yanai, Y Itoyama
Brain 2010;133(Pt 6):1772-1778