The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases
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Published:2023-10-27
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Smith RubenORCID, Capotosti FrancescaORCID, Schain Martin, Ohlsson Tomas, Vokali Efthymia, Molette JeromeORCID, Touilloux Tanja, Hliva ValerieORCID, Dimitrakopoulos Ioannis K., Puschmann Andreas, Jögi Jonas, Svenningsson PerORCID, Andréasson Mattias, Sandiego Christine, Russell David S.ORCID, Miranda-Azpiazu Patricia, Halldin Christer, Stomrud Erik, Hall SaraORCID, Bratteby KlasORCID, Tampio L’Estrade Elina, Luthi-Carter Ruth, Pfeifer Andrea, Kosco-Vilbois Marie, Streffer JohannesORCID, Hansson OskarORCID
Abstract
AbstractA positron emission tomography (PET) tracer detecting α-synuclein pathology will improve the diagnosis, and ultimately the treatment of α-synuclein-related diseases. Here we show that the PET ligand, [18F]ACI-12589, displays good in vitro affinity and specificity for pathological α-synuclein in tissues from patients with different α-synuclein-related disorders including Parkinson’s disease (PD) and Multiple-System Atrophy (MSA) using autoradiography and radiobinding techniques. In the initial clinical evaluation we include 23 participants with α-synuclein related disorders, 11 with other neurodegenerative disorders and eight controls. In vivo [18F]ACI-12589 demonstrates clear binding in the cerebellar white matter and middle cerebellar peduncles of MSA patients, regions known to be highly affected by α-synuclein pathology, but shows limited binding in PD. The binding statistically separates MSA patients from healthy controls and subjects with other neurodegenerative disorders, including other synucleinopathies. Our results indicate that α-synuclein pathology in MSA can be identified using [18F]ACI-12589 PET imaging, potentially improving the diagnostic work-up of MSA and allowing for detection of drug target engagement in vivo of novel α-synuclein targeting therapies.
Funder
Michael J. Fox Foundation for Parkinson's Research Vetenskapsrådet Knut och Alice Wallenbergs Stiftelse Alzheimerfonden Hjärnfonden Swedish Parkinson's Disease Association | Parkinsonfonden Cure Alzheimer's Fund Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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