title: A Practical One-Pot Synthesis of Positron Emission Tomography (PET) Tracers via Nickel-Mediated Radiofluorination.
abstract: Recently a novel method for the preparation of (18)F-labeled arenes via oxidative [(18)F]fluorination of easily accessible and sufficiently stable nickel complexes with [(18)F]fluoride under exceptionally mild reaction conditions was published. The suitability of this procedure for the routine preparation of clinically relevant positron emission tomography (PET) tracers, 6-[(18)F]fluorodopamine (6-[(18)F]FDA), 6-[(18)F]fluoro-l-DOPA (6-[(18)F]FDOPA) and 6-[(18)F]fluoro-m-tyrosine (6-[(18)F]FMT), was evaluated. The originally published base-free method was inoperative. However, a "low base" protocol afforded protected radiolabeled intermediates in radiochemical conversions (RCCs) of 5-18 %. The subsequent deprotection step proceeded almost quantitatively (>95 %). The simple one-pot two-step procedure allowed the preparation of clinical doses of 6-[(18)F]FDA and 6-[(18)F]FDOPA within 50 min (12 and 7 % radiochemical yield, respectively). In an unilateral rat model of Parkinsons disease, 6-[(18)F]FDOPA with high specific activity (175 GBq μmol(-1)) prepared using the described nickel-mediated radiofluorination was compared to 6-[(18)F]FDOPA with low specific activity (30 MBq μmol(-1)) produced via conventional electrophilic radiofluorination. Unexpectedly both tracer variants displayed very similar in vivo properties with respect to signal-to-noise ratio and brain distribution, and consequently, the quality of the obtained PET images was almost identical.
authors.affiliation: Institute of Radiochemistry & Experimental Molecular Imaging, University Clinic Cologne Kerpener Str. 62, 50937, Cologne, Germany ; Max Planck Institute for Metabolism Research Gleueler Str. 50, 50931, Cologne, Germany.
authors.forename: Boris D
authors.initials: BD
authors.lastname: Zlatopolskiy
authors.affiliation: Institute of Radiochemistry & Experimental Molecular Imaging, University Clinic Cologne Kerpener Str. 62, 50937, Cologne, Germany ; Max Planck Institute for Metabolism Research Gleueler Str. 50, 50931, Cologne, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zischler
authors.affiliation: Institute of Radiochemistry & Experimental Molecular Imaging, University Clinic Cologne Kerpener Str. 62, 50937, Cologne, Germany ; Max Planck Institute for Metabolism Research Gleueler Str. 50, 50931, Cologne, Germany ; Clinic of Nuclear Medicine, RWTH Aachen University Pauwelsstraße 30, 52074, Aachen, Germany.
authors.forename: Elizaveta A
authors.initials: EA
authors.lastname: Urusova
authors.affiliation: Institute of Radiochemistry & Experimental Molecular Imaging, University Clinic Cologne Kerpener Str. 62, 50937, Cologne, Germany ; Max Planck Institute for Metabolism Research Gleueler Str. 50, 50931, Cologne, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Endepols
authors.affiliation: Institute of Radiochemistry & Experimental Molecular Imaging, University Clinic Cologne Kerpener Str. 62, 50937, Cologne, Germany ; Max Planck Institute for Metabolism Research Gleueler Str. 50, 50931, Cologne, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Kordys
authors.affiliation: Institute of Organic & Biomolecular Chemistry, Georg-August University Tammannstr. 2, 37077, Göttingen, Germany.
authors.forename: Holm
authors.initials: H
authors.lastname: Frauendorf
authors.affiliation: Clinic of Nuclear Medicine, RWTH Aachen University Pauwelsstraße 30, 52074, Aachen, Germany ; Department of Nuclear Medicine, Maastricht University Medical Center PO Box 616, 6200, MD Maastricht, The Netherlands.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Institute of Radiochemistry & Experimental Molecular Imaging, University Clinic Cologne Kerpener Str. 62, 50937, Cologne, Germany ; Max Planck Institute for Metabolism Research Gleueler Str. 50, 50931, Cologne, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
keywords: [18F]fluoride; nucleophilic aromatic substitution; positron emission tomography (PET); radiopharmaceuticals; radiosynthesis