Amyloid-beta radiotracer [ 18 F]BF-227 does not bind to cytoplasmic glial inclusions of post-mortem Multiple System Atrophy brain tissue

Mathieu Verdurand (1) , Elise Levigoureux (1, 2) , Sophie Lancelot (1, 2) , Waël Zeinyeh (1, 3) , Thierry Billard (4, 3) , Isabelle Quadrio (1, 2) , Armand Perret-Liaudet (1, 2) , Luc Zimmer (1, 4, 2) , Fabien Chauveau (1)

1 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
2 Groupement Hospitalier Est, Hospices Civils de Lyon
3 SURCOOF - Synthèse, Utilisation, Réactivité des Composés Organiques et OrganoFluorés
4 CERMEP - imagerie du vivant - Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant

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 pre-mortem diagnosis tool would improve early diagnosis, and help monitoring disease progression and therapeutic efficacy. One Positron Emission Tomography (PET) study suggested [11C]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). [18F]BF-227, chemically identical to [11C]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 [18F]BF-227 to CGI at concentrations typically achieved in PET experiments.

Mots clés: radiotracer; synucleinopathies; alpha-synuclein; positron emission tomography; autoradiography; multiple system atrophy

Domaines: Imagerie; Neurosciences [q-bio.NC]

Mathieu Verdurand, Elise Levigoureux, Sophie Lancelot, Waël Zeinyeh, Thierry Billard, et al.. Amyloid-beta radiotracer [ 18 F]BF-227 does not bind to cytoplasmic glial inclusions of post-mortem Multiple System Atrophy brain tissue. Contrast Media and Molecular Imaging, 2018, 2018, ⟨10.1155/2018/9165458⟩. ⟨hal-01691091⟩