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Copper‐Mediated Aromatic Radiofluorination Revisited: Efficient Production of PET Tracers on a Preparative Scale
Author(s) -
Zlatopolskiy Boris D.,
Zischler Johannes,
Krapf Philipp,
Zarrad Fadi,
Urusova Elizaveta A.,
Kordys Elena,
Endepols Heike,
Neumaier Bernd
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201405586
Subject(s) - copper , scale (ratio) , chemistry , organic chemistry , physics , quantum mechanics
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.