A Novel Brain PET Radiotracer for Imaging Alpha Synuclein Fibrils in Multiple System Atrophy.

ABSTRACT: Abnormal α-synuclein (α-syn) aggregation characterizes α-synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy (MSA). However, no suitable positron emission tomography (PET) radiotracer for imaging α-syn in PD and MSA exists currently. Our structure-activity relationship studies identified 4-methoxy-N-(4-(3-(pyridin-2-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)phenyl)benzamide (4i) as a PET radiotracer candidate for imaging α-syn. In vitro assays revealed high binding of 4i to recombinant α-syn fibrils (inhibition constant (K_i) = 6.1 nM) and low affinity for amyloid beta (Aβ) fibrils in Alzheimer's disease (AD) homogenates. However, [³H]4i also exhibited high specific binding to AD, progres

SUBMITTER: Kim HY 

PROVIDER: S-EPMC10617560 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature