The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases

Ruben Smith, Francesca Capotosti, Martin Schain, Tomas Ohlsson, Efthymia Vokali, Jerome Molette, Tanja Touilloux, Valerie Hliva, Ioannis K. Dimitrakopoulos, Andreas Puschmann, Jonas Jögi, Per Svenningsson, Mattias Andréasson, Christine Sandiego, David S. Russell, Patricia Miranda-Azpiazu, Christer Halldin, Erik Stomrud, Sara Hall, Klas Bratteby, Elina Tampio L’Estrade, Ruth Luthi-Carter, Andrea Pfeifer, Marie Kosco-Vilbois, Johannes Streffer () and Oskar Hansson ()
Additional contact information
Ruben Smith: Lund University
Francesca Capotosti: EPFL Innovation Park
Martin Schain: Lund University
Tomas Ohlsson: Skånes University Hospital
Efthymia Vokali: EPFL Innovation Park
Jerome Molette: EPFL Innovation Park
Tanja Touilloux: EPFL Innovation Park
Valerie Hliva: EPFL Innovation Park
Ioannis K. Dimitrakopoulos: EPFL Innovation Park
Andreas Puschmann: Skåne University Hospital
Jonas Jögi: Skåne University Hospital
Per Svenningsson: Karolinska University Hospital
Mattias Andréasson: Karolinska University Hospital
Christine Sandiego: Invicro, LLC
David S. Russell: Invicro, LLC
Patricia Miranda-Azpiazu: Karolinska Institute
Christer Halldin: Karolinska Institute
Erik Stomrud: Lund University
Sara Hall: Lund University
Klas Bratteby: Skånes University Hospital
Elina Tampio L’Estrade: Skånes University Hospital
Ruth Luthi-Carter: EPFL Innovation Park
Andrea Pfeifer: EPFL Innovation Park
Marie Kosco-Vilbois: EPFL Innovation Park
Johannes Streffer: EPFL Innovation Park
Oskar Hansson: Lund University

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract A 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.

Date: 2023
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DOI: 10.1038/s41467-023-42305-3

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