The accumulation of hyperphosphorylated tau protein in the brain is regarded as one of the hallmarks of Alzheimer's disease (AD). In vivo imaging of tau aggregates is helpful for diagnosis and monitoring of the progression of AD. In this study, we designed and synthesized novel radioiodinated benzimidazopyrimidine (BIPM) and pyridoimidazopyridine (PIP) derivatives with a monomethylamino, monoethylamino, monopropylamino, or diethylamino group as tau imaging probes for single-photon-emission computed tomography (SPECT). On in vitro autoradiography with AD brain sections, [ 125 I]PIP-NHMe showed the highest selective binding affinity for tau aggregates among the radioiodinated BIPM and PIP derivatives. In a biodistribution study using normal mice, [ 125 I]PIP-NHMe and [ 125 I]PIP-NHEt displayed high initial uptake (6.62 and 6.86% ID/g, respectively, at 2 min postinjection) into and rapid clearance from the brain, with brain 2 min /brain 30 min ratios of 38.9 and 28.6, respectively. These results suggest that [ 123 I]PIP-NHMe may be a novel SPECT probe that is useful for detecting tau aggregates in the AD brain.