Amyloid-Beta Radiotracer [F]BF-227 Does Not Bind to Cytoplasmic Glial Inclusions of Postmortem Multiple System Atrophy Brain Tissue.

Contrast Media Mol Imaging 2018 6;2018:9165458. Epub 2018 Feb 6.

Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.

The accumulation of aggregated alpha-synuclein (-syn) in multiple brain regions is a neuropathological hallmark of synucleinopathies. Multiple system atrophy (MSA) is a synucleinopathy characterized by the predominant cerebral accumulation of aggregated -syn as cytoplasmic glial inclusions (CGI). A premortem diagnosis tool would improve early diagnosis and help monitoring disease progression and therapeutic efficacy. One Positron Emission Tomography (PET) study suggested [C]BF-227 as a promising radiotracer for monitoring intracellular -syn deposition in MSA patients. We sought to confirm the binding of this radiotracer to -syn using state-of-the-art autoradiography. Medulla sections were obtained from 9 MSA patients and 9 controls (London Neurodegenerative Diseases Brain Bank). [F]BF-227, chemically identical to [C]BF-227, was used at nanomolar concentrations to perform autoradiography assays. Autoradiograms were superimposed on fluorescent staining from the conformational anti--syn antibody 5G4 and quantified after immunofluorescence-driven definition of regions of interest. Autoradiography showed no specific signals in MSA patients in comparison to controls despite widespread pathology detected by immunofluorescence. Autoradiography does not support a significant binding of [F]BF-227 to CGI at concentrations typically achieved in PET experiments.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818909PMC
July 2019

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