title: A concise radiosynthesis of the tau radiopharmaceutical, [(18) F]T807.
abstract: Fluorine-18 labeled 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([(18) F]T807) is a potent and selective agent for imaging paired helical filaments of tau and is among the most promising PET radiopharmaceuticals for this target in early clinical trials. The present study reports a simplified one-step method for the synthesis of [(18) F]T807 that is broadly applicable for routine clinical production using a GE TRACERlab™ FXFN radiosynthesis module. Key facets of our optimized radiosynthesis include development and use of a more soluble protected precursor, tert-butyl 7-(6-nitropyridin-3-yl)-5H-pyrido[4,3-b]indole-5-carboxylate, as well as new HPLC separation conditions that enable a facile one-step synthesis. During the nucleophilic fluorinating reaction with potassium cryptand [(18) F]fluoride (K[(18) F]/K222 ) in DMSO at 130 °C over 10 min the precursor is concurrently deprotected. Formulated [(18) F]T807 was prepared in an uncorrected radiochemical yield of 14 ± 3%, with a specific activity of 216 ± 60 GBq/µmol (5837 ± 1621 mCi/µmol) at the end of synthesis (60 min; n = 3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation that we anticipate will facilitate widespread clinical use of [(18) F]T807.
authors: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 55 Fruit St., White 427, Boston, MA, 02114, USA; Department of Radiology, Harvard Medical School, 55 Fruit St., White 427, Boston, MA, 02114, USA.
authors: Timothy M
authors: TM
authors: Shoup
authors: Daniel L
authors: DL
authors: Yokell
authors: Peter A
authors: PA
authors: Rice
authors: Raul N
authors: RN
authors: Jackson
authors: Eli
authors: E
authors: Livni
authors: Keith A
authors: KA
authors: Johnson
authors: Thomas J
authors: TJ
authors: Brady
authors: Neil
authors: N
authors: Vasdev
mesh_terms: D002243:Carbolines / Q000138:chemical synthesis*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D002243:Carbolines; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D016875:tau Proteins; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
keywords: PET; T807; fluorine-18; tau