title: First human use of a radiopharmaceutical prepared by continuous-flow microfluidic radiofluorination: proof of concept with the tau imaging agent [18F]T807.
abstract: Despite extensive preclinical imaging with radiotracers developed by continuous-flow microfluidics, a positron emission tomographic (PET) radiopharmaceutical has not been reported for human imaging studies by this technology. The goal of this study was to validate the synthesis of the tau radiopharmaceutical 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([18F]T807) and perform first-in-human PET scanning enabled by microfluidic flow chemistry. [18F]T807 was synthesized by our modified one-step method and adapted to suit a commercial microfluidic flow chemistry module. For this proof of concept, the flow system was integrated to a GE Tracerlab FXFN unit for high-performance liquid chromatography purification and formulation. Three consecutive productions of [18F]T807 were conducted to validate this radiopharmaceutical. Uncorrected radiochemical yields of 17 ± 1% of crude [18F]T807 (≈ 500 mCi, radiochemical purity 95%) were obtained from the microfluidic device. The crude material was then purified, and > 100 mCi of the final product was obtained in an overall uncorrected radiochemical yield of 5 ± 1% (n  =  3), relative to starting [18F]fluoride (end of bombardment), with high radiochemical purity (≥ 99%) and high specific activities (6 Ci/μmol) in 100 minutes. A clinical research study was carried out with [18F]T807, representing the first reported human imaging study with a radiopharmaceutical prepared by this technology.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Liang
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Yokell
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.forename: Peter A
authors.initials: PA
authors.lastname: Rice
authors.forename: Raul N
authors.initials: RN
authors.lastname: Jackson
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Shoup
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Brady
authors.forename: Georges
authors.initials: G
authors.lastname: El Fakhri
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Collier
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D002243:Carbolines / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D044085:Microfluidics / Q000295:instrumentation; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*
chemical_list: D002243:Carbolines; D019275:Radiopharmaceuticals; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole