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 [(18)F]fluoro-pegylated 2-phenylquinoxaline derivatives, 2-(4-(2-[(18)F]fluoroethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4a) and 2-(4-(2-(2-(2-[(18)F]fluoroethoxy)ethoxy)ethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4b) were prepared. Both of them displayed high binding affinity to Aβ(1-42) aggregates (K(i) = 10.0 ± 1.4 nM for 4a, K(i) = 5.3 ± 3.2 nM for 4b). The specific and high binding of [(18)F]4a and [(18)F]4b to Aβ plaques was confirmed by in vitro autoradiography on brain sections of AD human and transgenic mice. In biodistribution in normal mice, [(18)F]4a displayed high initial brain uptake (8.17% ID/g at 2 min) and rapid washout from the brain. These preliminary results suggest [(18)F]4a may be a potential PET imaging agent for Aβ plaques in the living human brain.