Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging β‑Amyloid in Alzheimer’s Disease Affected Brain

In this study, we synthesized of a series of 2-phenyl- and 2-pyridyl-imidazo­[1,2-a]­pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of β-amyloid (Aβ). Among the 11 evaluated compounds, 10 showed moderate affinity to Aβ(1–42) aggregates, exhibiting half-maximal inhibitory concentrations (IC50) of 14.7 ± 6.07–87.6 ± 39.8 nM. In vitro autoradiography indicated that 123I-labeled triazole-substituted derivatives displayed highly selective binding to Aβ plaques in the hippocampal region of Alzheimer’s disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all 123I-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging Aβ plaques, with the highest selectivity observed for a 1H-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [123I]­ABC577. This compound showed good kinetics in rat brain as well as moderate in vivo stability in rats and is thus a promising SPECT imaging probe for AD in clinical settings.