A report of the automated radiosynthesis of the tau positron emission tomography radiopharmaceutical, [¹⁸ F]-THK-5351

The radiotracer, [¹⁸ F]-THK-5351, is a highly selective and high-binding affinity PET imaging agent for aggregates of hyper-phosphorylated tau protein. Our report is a simplified 1-pot, 2-step radiosynthesis of [¹⁸ F]-THK-5351. This report is broadly applicable for routine clinical production and multi-center trials on account of favorable half-life of flourine-18 and the use of a commercially available radiosynthesis module, the GE TRACERlab™ FX_FN . First, the O-THP protected tosyl precursor underwent nucleophilic fluorinating reaction with potassium cryptand fluoride ([¹⁸ F] fluoride (K[¹⁸ F]/K₂₂₂ )) in Dimethyl sulfoxide at 110°C for 10 minutes followed by O-THP removal by using diluted hydrochloric acid (HCl) at same temperature. [¹⁸ F]-THK-5351 was purified via semi-preparative high-performance liquid chromatography and formulated by using 10% EtOH, United States Pharmacopeia (USP) in 0.9% sodium chloride for injection, USP and an uncorrected radiochemical yield of 21 ± 3.5%, with a specific activity of 153.11 ± 25.9 GBq/μmol (4138 ± 700 mCi/μmol) at the end of synthesis (63 minutes; n = 3).