|
Title
|
|
|
|
The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| A positron emission tomography (PET) tracer detecting alpha-synuclein pathology will improve the diagnosis, and ultimately the treatment of alpha-synuclein-related diseases. Here we show that the PET ligand, [18F]ACI-12589, displays good in vitro affinity and specificity for pathological alpha-synuclein in tissues from patients with different alpha-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 alpha-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 alpha-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 alpha-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 alpha-synuclein targeting therapies. A PET tracer for alpha-synuclein would help diagnosis and treatment of alpha-syn-related diseases. Here the authors show that ACI-12589 shows an uptake in the cerebellar white matter in patients with multiple-system atrophy. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Nature communications
| |
|
Publication
|
|
|
|
2023
| |
|
ISSN
|
|
|
|
2041-1723
| |
|
DOI
|
|
|
|
10.1038/S41467-023-42305-3
| |
|
Volume/pages
|
|
|
|
14
:1
(2023)
, p. 1-12
| |
|
Article Reference
|
|
|
|
6750
| |
|
ISI
|
|
|
|
001091497000016
| |
|
Pubmed ID
|
|
|
|
37891183
| |
|
Medium
|
|
|
|
E-only publicatie
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|