title: A report of the automated radiosynthesis of the tau positron emission tomography radiopharmaceutical, [18F]-THK-5351.
abstract: 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).
authors.affiliation: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.|Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Neelamegam
authors.affiliation: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.|Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Yokell
authors.affiliation: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Rice
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Furumoto
authors.affiliation: Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.affiliation: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.|Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Georges
authors.initials: G
authors.lastname: El Fakhri
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis* / Q000737:chemistry; D001331:Automation / Q000379:methods; D060326:Chemistry Techniques, Synthetic / Q000379:methods; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000631:Aminopyridines; D011804:Quinolines; D019275:Radiopharmaceuticals; C000608225:THK5351
keywords: PET; THK-5351; Tau; fluorine-18