title: Copper-mediated aromatic radiofluorination revisited: efficient production of PET tracers on a preparative scale.
abstract: Two novel methods for copper-mediated aromatic nucleophilic radiofluorination were recently reported. Evaluation of these methods reveals that, although both are efficient in small-scale experiments, they are inoperative for the production of positron emission tomography (PET) tracers. Since high base content turned out to be responsible for low radiochemical conversions, a "low base" protocol has been developed which affords (18)F-labeled arenes from diaryliodonium salts and aryl pinacol boronates in reasonable yields. Furthermore, implementation of our "minimalist" approach to the copper-mediated [(18)F]-fluorination of (mesityl)(aryl)iodonium salts allows the preparation of (18)F-labeled arenes in excellent RCCs. The novel radiofluorination method circumvents time-consuming azeotropic drying and avoids the utilization of base and other additives, such as cryptands. Furthermore, this procedure enables the production of clinically relevant PET tracers; [(18)F]FDA, 4-[(18)F]FPhe, and [(18)F]DAA1106 are obtained in good isolated radiochemical yields. Additionally, [(18)F]DAA1106 has been evaluated in a rat stroke model and demonstrates excellent potential for visualization of translocator protein 18 kDa overexpression associated with neuroinflammation after ischemic stroke.
authors.affiliation: Institute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne, Kerpener Str. 62, 50937 Cologne (Germany), Fax: (+49) 221-47886851; Max Planck Institute for Metabolism Research, Gleueler Str. 50, 50931 Cologne (Germany).
authors.forename: Boris D
authors.initials: BD
authors.lastname: Zlatopolskiy
authors.forename: Johannes
authors.initials: J
authors.lastname: Zischler
authors.forename: Philipp
authors.initials: P
authors.lastname: Krapf
authors.forename: Fadi
authors.initials: F
authors.lastname: Zarrad
authors.forename: Elizaveta A
authors.initials: EA
authors.lastname: Urusova
authors.forename: Elena
authors.initials: E
authors.lastname: Kordys
authors.forename: Heike
authors.initials: H
authors.lastname: Endepols
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D054879:Halogenation; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D020521:Stroke / Q000000981:diagnostic imaging
chemical_list: D005462:Fluorine Radioisotopes; D006841:Hydrocarbons, Aromatic; D003300:Copper
keywords: copper; fluorination; imaging agents; positron emission tomography; radiopharmaceuticals