Technetium-99m Labeled Pyridyl Benzofuran Derivatives as Single Photon Emission Computed Tomography Imaging Probes for β-Amyloid Plaques in Alzheimer’s Brains

Three novel (99m)Tc-labeled pyridyl benzofuran derivatives were tested as potential probes for imaging β-amyloid plaques using single photon emission computed tomography (SPECT). The (99m)Tc and corresponding rhenium complexes were synthesized with bis(aminoethanethiol) (BAT) as a chelating ligand. All Re complexes showed affinity for Aβ(1-42) aggregates (K(i) = 13.6-149.6 nM). Biodistribution experiments in normal mice revealed that the (99m)Tc-labeled derivatives displayed sufficient uptake in the brain (1.41-1.80% ID/g at 2 min postinjection). Notably, [(99m)Tc]BAT-Bp-2 showed a good initial uptake (1.80% ID/g at 2 min) and a reasonable washout from the brain (0.79% ID/g at 60 min). Ex vivo autoradiography with [(99m)Tc]BAT-Bp-2 revealed substantial labeling of β-amyloid plaques in sections of brain tissue from Tg2576 transgenic mice but not in the age-matched controls. [(99m)Tc]BAT-Bp-2 may be a potential SPECT probe for imaging β-amyloid plaques in Alzheimer's brains.