title: Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor.
abstract: 6-[(18)F]Fluorodopamine (6-[(18) F]F-DA) is a positron emission tomography radiopharmaceutical used to image sympathetic cardiac innervation and neuroendocrine tumors. Imaging with 6-[(18)F]F-DA is constrained, in part, by the bioactivity and neurotoxicity of 6-[(19)F]fluorodopamine. Furthermore, routine access to this radiotracer is limited by the inherent difficulty of incorporation of [(18)F]fluoride into electron-rich aromatic substrates. We describe the simple and direct preparation of high specific activity (SA) 6-[(18)F]F-DA from no-carrier-added (n.c.a.) [(18)F]fluoride. Incorporation of n.c.a. [(18)F]fluoride into a diaryliodonium salt precursor was achieved in 50-75% radiochemical yields (decay corrected to end of bombardment). Synthesis of 6-[(18)F]F-DA on the IBA Synthera® and GE TRACERlab FX-FN automated platforms gave 6-[(18)F]F-DA in >99% chemical and radiochemical purities after HPLC purification. The final non-corrected yields of 6-[(18)F]F-DA were 25 ± 4% (n = 4, 65 min) and 31 ± 6% (n = 3, 75 min) using the Synthera and TRACERlab modules, respectively. Efficient access to high SA 6-[(18)F]F-DA from a diaryliodonium salt precursor and n.c.a. [(18)F]fluoride is provided by a relatively subtle change in reaction conditions - replacement of a polar aprotic solvent (acetonitrile) with a relatively nonpolar solvent (toluene) during the critical radiofluorination reaction. Implementation of this process on common radiochemistry platforms should make 6-[(18)F]F-DA readily available to the wider imaging community.
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Kiel D
authors.initials: KD
authors.lastname: Neumann
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Linlin
authors.initials: L
authors.lastname: Qin
authors.affiliation: Division of Nuclear Medicine, Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Vāvere
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
authors.affiliation: Division of Nuclear Medicine, Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Barry L
authors.initials: BL
authors.lastname: Shulkin
authors.affiliation: Division of Nuclear Medicine, Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Snyder
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: DiMagno
mesh_terms: D060326:Chemistry Techniques, Synthetic / Q000295:instrumentation / Q000379:methods; D004298:Dopamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D009861:Onium Compounds / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
chemical_list: D009861:Onium Compounds; D019275:Radiopharmaceuticals; C029253:6-fluorodopamine; D004298:Dopamine
keywords: 6-[18F]fluorodopamine; diaryliodonium salts; emission computed tomography; fluorine-18; positron emission tomography