Skip to Main content Skip to Navigation
Journal articles

In Silico, in Vitro, and in Vivo Evaluation of New Candidates for α-Synuclein PET Imaging

Abstract : Accumulation of α-synuclein (α-syn) is a neuropathological hallmark of synucleinopathies. To date, no selective α-syn positron emission tomography (PET) radiotracer has been identified. Our objective was to develop the first original, selective, and specific α-syn PET radiotracer. Chemical design inspired from three structural families that demonstrated interesting α-syn binding characteristics was used as a starting point. Bioinformatics modeling of α-syn fibrils was then employed to select the best molecular candidates before their syntheses. An in vitro binding assay was performed to evaluate the affinity of the compounds. Radiotracer specificity and selectivity were assessed by in vitro autoradiography and in vivo PET studies in animal (rodents) models. Finally, gold standard in vitro autoradiography with patients’ postmortem tissues was performed to confirm/infirm the α-syn binding characteristics. Two compounds exhibited a good brain availability and bound to α-syn and Aβ fibrils in a rat model. In contrast, no signal was observed in a mouse model of synucleinopathy. Experiments in human tissues confirmed these negative results.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-01955442
Contributor : Béatrice Rayet Connect in order to contact the contributor
Submitted on : Friday, December 14, 2018 - 1:00:42 PM
Last modification on : Wednesday, November 3, 2021 - 7:05:42 AM

Identifiers

  • HAL Id : hal-01955442, version 1

Citation

Mathieu Verdurand, Elise Levigoureux, Wael Zeinyeh, Laurent Berthier, Meriem Mendjel-Herda, et al.. In Silico, in Vitro, and in Vivo Evaluation of New Candidates for α-Synuclein PET Imaging. Molecular Pharmaceutics, American Chemical Society, 2018, 15 (8), pp.3153-3166. ⟨hal-01955442⟩

Share

Metrics

Les métriques sont temporairement indisponibles