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.
Original language | English (US) |
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Pages (from-to) | 51-58 |
Number of pages | 8 |
Journal | European Journal of Medicinal Chemistry |
Volume | 57 |
DOIs | |
State | Published - Nov 2012 |
Keywords
- β-Amyloid plaque
- 2-Phenylquinoxaline
- Alzheimer's disease
- Autoradiography
- Biodistribution
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
- Organic Chemistry