Amyloid-Beta Radiotracer [18F]BF-227 Does Not Bind to Cytoplasmic Glial Inclusions of Postmortem Multiple System Atrophy Brain Tissue. (6th February 2018)

• Record Type: Journal Article
• Authors: Verdurand, Mathieu; Levigoureux, Elise; Lancelot, Sophie; Zeinyeh, Waël; Billard, Thierry; Quadrio, Isabelle; Perret-Liaudet, Armand; Zimmer, Luc; Chauveau, Fabien
• Other Names: Schirrmacher Ralf Academic Editor.
• Is Part Of: Contrast media & molecular imaging. Volume 2018(2018)
• Publication Date: 2018-02-06
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1155/2018/9165458
• Languages: English
• ISSNs: 1555-4309

Abstract

Abstract : The accumulation of aggregated alpha-synuclein ( α -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 α -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 [ 11 C]BF-227 as a promising radiotracer for monitoring intracellular α -syn deposition in MSA patients. We sought to confirm the binding of this radiotracer to α -syn using state-of-the-art autoradiography. Medulla sections were obtained from 9 MSA patients and 9 controls (London Neurodegenerative Diseases Brain Bank). [ 18 F]BF-227, chemically identical to [ 11 C]BF-227, was used at nanomolar concentrations to perform in vitro autoradiography assays. Autoradiograms were superimposed on fluorescent staining from the conformational anti- α -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 [ 18 F]BF-227 to CGI at concentrations typically achieved in PET experiments.