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Abstract: Four 99mTc-labeled dibenzylideneacetone derivatives and corresponding rhenium complexes were successfully synthesized and biologically evaluated as potential imaging probes for Aβ plaques using SPECT. All rhenium complexes (5a–d) showed affinity for Aβ (1–42) aggregates (K i = 13.6–120.9 nM), and selectively stained the Aβ plaques on brain sections of transgenic mice. Biodistribution in normal mice revealed that [99mTc]5a–d exhibited moderate initial uptake (0.31%–0.49% ID/g at 2 min) and reasonable brain washout at 60 min post-injection. Although additional optimizations are still needed to facilitate it's penetration through BBB, the present results indicate that [99mTc]5a may be a potential SPECT probe for imaging Aβ plaques in Alzheimer's brains. [Copyright &y& Elsevier]

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 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 [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. [Copyright &y& Elsevier]