title: Fully automated synthesis of [(18)F]T807, a PET tau tracer for Alzheimer's disease.
abstract: The authentic standard T807 and its nitro-precursor T807P as well as t-Boc-protected T807P precursor for radiolabeling were synthesized from (4-bromophenyl)boronic acid, 3-bromo-4-nitropyridine and 3-bromo-6-nitropyridine with overall chemical yield 27% in three steps, 4-7% in three to five steps, and 3-8% in four to five steps, respectively. [(18)F]T807 was synthesized from T807P by the nucleophilic [(18)F]fluorination with K[(18)F]F/Kryptofix 2.2.2 in DMSO at 140 °C followed by reduction with Fe powder/HCOOH through manual synthesis with 5-10% decay corrected radiochemical yield in two steps. [(18)F]T807 was also synthesized from t-Boc-protected T807P by a concurrent [(18)F]fluorination and deprotection with K[(18)F]F/Kryptofix 2.2.2 in DMSO at 140 °C and purified by HPLC-SPE method in a home-built automated [(18)F]radiosynthesis module with 20-30% decay corrected radiochemical yield in one step. The specific activity of [(18)F]T807 at end of bombardment (EOB) was 37-370 GBq/μmol.
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA. Electronic address: qzheng@iupui.edu.
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D054879:Halogenation; D006801:Humans; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D016875:tau Proteins / Q000032:analysis*
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: Alzheimer’s disease (AD); Automation; Positron emission tomography (PET); Tau tracer; [(18)F]T807