18F-Labeled 2-phenylquinoxaline derivatives as potential positron emission tomography probes for in vivo imaging of β-amyloid plaques

Abstract

In continuation of our study on the 2-phenylquinoxaline scaffold as potential β-amyloid imaging probes, two [18F]fluoro-pegylated 2-phenylquinoxaline derivatives, 2-(4-(2-[18F]fluoroethoxy)phenyl)-N- methylquinoxalin-6-amine ([18F]4a) and 2-(4-(2-(2-(2-[ 18F]fluoroethoxy)ethoxy)ethoxy)phenyl)-N-methylquinoxalin-6-amine ([18F]4b) were prepared. Both of them displayed high binding affinity to Aβ1-42 aggregates (Ki = 10.0 ± 1.4 nM for 4a, Ki = 5.3 ± 3.2 nM for 4b). The specific and high binding of [18F]4a and [18F]4b to Aβ plaques was confirmed by in vitro autoradiography on brain sections of AD human and transgenic mice. In biodistribution in normal mice, [18F]4a displayed high initial brain uptake (8.17% ID/g at 2 min) and rapid washout from the brain. These preliminary results suggest [18F]4a may be a potential PET imaging agent for Aβ plaques in the living human brain. © 2012 Elsevier Masson SAS. All rights reserved.