Synthesis and biological evaluation of novel technetium-99m-labeled phenylquinoxaline derivatives as single photon emission computed tomography imaging probes targeting β-amyloid plaques in Alzheimer's disease

Abstract

The development of an imaging probe targeting β-amyloid (Aβ) plaques in Alzheimer's disease labeled with technetium-99m, the most commonly used radioisotope for clinical diagnoses, has been strongly anticipated. In this study, we synthesized three novel ^99mTc complexes with the phenylquinoxaline scaffold and evaluated their properties for imaging Aβ plaques. The ^99mTc and corresponding Re complexes were synthesized with bis(aminoethanethiol) (BAT) as a chelating ligand. In a binding affinity assay using recombinant Aβ(1–42) aggregates in vitro, the ^99mTc-labeled N,N-dimethylated phenylquinoxaline derivative (^99mTc-BAT-C3-PQ-1) and the corresponding Re complex showed sufficient affinity for Aβ(1–42) aggregates. An in vivo biodistribution study in normal mice revealed that ^99mTc-BAT-C3-PQ-1 showed a moderate initial brain uptake and a reasonable clearance from the brain. An ex vivo autoradiographic examination with ^99mTc-BAT-C3-PQ-1 showed the marked labeling of Aβ plaques in brain sections from Tg2576 transgenic mice but not age-matched controls. ^99mTc-BAT-C3-PQ-1 may be a potential single photon emission computed tomography probe for imaging Aβ plaques in Alzheimer's disease.