The development of a PET radiotracer for imaging alpha synuclein aggregates in Parkinson's disease.

ABSTRACT: M503-1619 was identified as a promising ligand for positron emission tomography (PET) imaging of α-synuclein (α-Syn) pathology in Parkinson's disease (PD). An exemplar for binding site 9 (residues GLY-86, ILE-88, PHE-94 and LYS-96) of α-Syn fibrils was generated. An in silico ultrahigh throughput screening campaign was conducted using a 42 million compound library. Secondary in silico methods followed by visual inspection were used to select 6 compounds as candidates for in vitro binding studies. M503-1619 was found to have a high binding affinity (K _i = 6.5 nM versus the site 9 radioligand [³H]BF-2846) to α-Syn fibrils and low affinity for beta amyloid (K _i = 390 nM versus [³H]PiB) i

SUBMITTER: Tian GL 

PROVIDER: S-EPMC12004261 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature