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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.

rsc advances

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