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

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 60; no. 2; pp. 140 - 146
• Main Authors: Neelamegam, Ramesh, Yokell, Daniel L., Rice, Peter A., Furumoto, Shozo, Kudo, Yukitsuka, Okamura, Nobuyuki, El Fakhri, Georges
• Format: Journal Article
• Language: English; French; German
• Published: England Wiley Subscription Services, Inc 01.02.2017
• Subjects: Aminopyridines - chemical synthesis; Aminopyridines - chemistry; Automation - methods; Chemistry Techniques, Synthetic - methods; fluorine‐18; PET; Quinolines - chemical synthesis; Quinolines - chemistry; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Tau; THK‐5351; THK-5351; Tau; fluorine-18; PET
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3482

The radiotracer, [18F]‐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 [18F]‐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™ FXFN. First, the O‐THP protected tosyl precursor underwent nucleophilic fluorinating reaction with potassium cryptand fluoride ([18F] fluoride (K[18F]/K222)) in Dimethyl sulfoxide at 110°C for 10 minutes followed by O‐THP removal by using diluted hydrochloric acid (HCl) at same temperature. [18F]‐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). This work presents the cGMP radiopharmaceutical validation of the tau positron emission tomography (PET) radiopharmaceutical [18F]‐THK‐5351 on the GE Tracerlab FX‐FN. We reported an uncorrected radiochemical yield of 21 ± 3.5%, with a pecific activity of 153.11 ± 25.9 GBq/μmol (4138 ± 700 mCi/μmol) at the end of synthesis (63 min; n = 3).