Improved preparation and chemical kinetics on fully automated synthesis of [¹⁸F]-THK523, a PET imaging probe for Tau pathologies

Extensive accumulation of neurofibrillary tangles (NFTs) consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimer’s disease. However, no PET probe is currently available for selective detection of NFTs in the living human brain. [18F]-THK523 was developed as a potential in vivo imaging probe for tau pathology. In this paper, we report a new protected precursor, 2-((2-(4-(( tert-butoxycarbonyl)amino)phenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate (THK-7), instead of 2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate (BF241), and an improved automated radiosynthesis of [18F]-THK523 and the study on chemical kinetics of the labeling reaction of [18F]-THK523, with high-yield (70±5%, n=6, decay-corrected to end of bombardment), and high radiochemical purity (>90%) and specific activity (2.5 ± 0.5 Ci/μmol) from protected precursor on fully automated module at the end of radiosynthesis (45–55 min). The chemical kinetics for [18F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.