Synthesis and Preliminary Clinical Application of Tau Protein Imaging Agent ¹⁸F-THK5317

We report automatic synthesis and biological evaluation of 6-(3-¹⁸Ffluoro-2-hydroxy)propoxy-2-(4-methylaminophenyl)quinoline ((S) ¹⁸F-THK5117, or ¹⁸F-THK5317), a novel PET tracer for Tau protein imaging in vivo. ¹⁸F-THK5317 was prepared from (2-(4-methylaminophenyl)-6-2-(tetrahydro-2H-pyran-2-yloxy)-3-tosyloxy-propoxyquinoline) via nucleophilic substitution, acid-hydrolysis, alkali neutralization and HPLC purification, two methods of treatment of rough product were used. Biodistribution study in the KM mice was performed. The discrepancy of PET/MR imaging characteristics of ¹⁸F-THK5317 in normal control and Alzheimer’s subjects was contrasted and analyzed. Pre-purification of crude product by C18 SPE column before HPLC separation increased the quantity of ¹⁸F-THK5317 and enhanced its radio-chemical purity. The undecay corrected radio-chemical yield was （18.7±5.3）% （n=7）, the radio-chemical purity was more than 95%, and the product showed good stability at room temperature. Bio-distribution of the ¹⁸F-THK5317 in mice indicates that initial uptake was high in brain, and radioactivity was quickly washed out from normal brain with the Brain_{1 min}/Brain_{60 min} ratio of 34. In vivo study in AD dementia patient using ¹⁸F-THK5317 has shown considerable cortical uptake and temporal lobe retention, in comparison to HC individual. These findings suggested that ¹⁸F-THK5317 could be an excellent imaging agent for tau protein in AD patients.