18F-labeled benzimidazopyridine derivatives for PET imaging of tau pathology in Alzheimer's disease.

Hyperphosphorylated tau proteins are one of the neuropathological hallmarks in the Alzheimer's disease (AD) brain. The in vivo imaging of tau aggregates with nuclear medical imaging probes is helpful for the further comprehension of and medical intervention in the AD pathology. For tau-selective PET imaging, we newly designed and synthesized 18F-labeled benzimidazopyridine (BIP) derivatives with fluoroalkylamino groups, [18F]IBIPF1 and [18F]IBIPF2, and evaluated their utilities as tau imaging probes. They both bound selectively to tau against amyloid β (Aβ) aggregates in AD brain sections in vitro, and showed good pharmacokinetics in mouse brains in vivo. Notably, [18F]IBIPF1 exhibited high tau-selectivity (Tau/Aβ ratio = 34.8), high brain uptake (6.22% ID/g at 2 min postinjection), and subsequent washout (2.77% ID/g at 30 min postinjection). In vivo analysis of radiometabolites indicated that [18F]IBIPF1 was stable against metabolism in the mouse brain. These encouraging preclinical results suggest that further structural optimization based on the BIP scaffold may lead to the development of more useful tau imaging probes.