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

Smith, Ruben LU ; Capotosti, Francesca ; Schain, Martin LU ; Ohlsson, Tomas ; Vokali, Efthymia ; Molette, Jerome ; Touilloux, Tanja ; Hliva, Valerie ; Dimitrakopoulos, Ioannis K. and Puschmann, Andreas LU orcid , et al. (2023) In Nature Communications 14(1).
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... (More)

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.

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type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
14
issue
1
article number
6750
publisher
Nature Publishing Group
external identifiers
  • pmid:37891183
  • scopus:85174956785
ISSN
2041-1723
DOI
10.1038/s41467-023-42305-3
language
English
LU publication?
yes
id
85e7b22c-58cd-436d-a47e-5894ff96e83b
date added to LUP
2024-01-11 15:35:21
date last changed
2024-04-26 12:25:38
@article{85e7b22c-58cd-436d-a47e-5894ff96e83b,
  abstract     = {{<p>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, [<sup>18</sup>F]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 [<sup>18</sup>F]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 [<sup>18</sup>F]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.</p>}},
  author       = {{Smith, Ruben and Capotosti, Francesca and Schain, Martin and Ohlsson, Tomas and Vokali, Efthymia and Molette, Jerome and Touilloux, Tanja and Hliva, Valerie and Dimitrakopoulos, Ioannis K. and Puschmann, Andreas and Jögi, Jonas and Svenningsson, Per and Andréasson, Mattias and Sandiego, Christine and Russell, David S. and Miranda-Azpiazu, Patricia and Halldin, Christer and Stomrud, Erik and Hall, Sara and Bratteby, Klas and Tampio L’Estrade, Elina and Luthi-Carter, Ruth and Pfeifer, Andrea and Kosco-Vilbois, Marie and Streffer, Johannes and Hansson, Oskar}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases}},
  url          = {{http://dx.doi.org/10.1038/s41467-023-42305-3}},
  doi          = {{10.1038/s41467-023-42305-3}},
  volume       = {{14}},
  year         = {{2023}},
}