Early noninvasive visualization of cerebral β-amyloid (Aβ) plaques with positron emission tomography (PET) is the most feasible way to diagnose Alzheimer's disease (AD). In this study, a series of flexible benzyldiamine derivatives (BDA) were proposed for binding to aggregated β-amyloid 1-42 (Aβ1-42) with high adaptability, high binding affinity (6.8 ± 0.6 nM), and rapid body excretion. The methylthio (12) and ethoxyl (10) derivatives were further labeled with 18F directly on their benzene ring and examined as PET probes for Aβ plaque imaging. [18F]12 displayed 4.87 ± 0.52% ID/g initial uptake and prompt washout from normal brain in biodistribution studies. MicroPET-CT imaging indicated sufficient retention of [18F]12 but lower white matter uptake in the brain of an AD transgenic mouse model compared with that of commercial [18F]AV-45. Our experimental results provide new insights for developing targeting ligands possessing a flexible framework for use as efficient Aβ probes for PET imaging of AD brain.