2-[F-18] Fluorophenylalanine: Synthesis by Nucleophilic F-18-Fluorination and Preliminary Biological Evaluation

2-[F-18]Fluorophenylalanine (2-[F-18]FPhe), a promising PET tracer for imaging of cerebral infarction and tumors, was efficiently prepared from an easily accessible iodonium salt precursor using Cu-mediated radiofluorination under 'low base' or 'minimalist' conditions. Whereas significant racemization was initially observed if the 'minimalist' protocol was applied for radiolabeling, it was completely suppressed by the careful adjustment of F-18(-) preprocessing. The initial biological study revealed a higher uptake of 2-[F-18]FPhe in different tumor cells in comparison to that of [F-18]FET. In contrast to 4-[F-18]FPhe, which suffered from rapid defluorination in vivo, 2-[F-18]FPhe demonstrated a sufficient in vivo stability. Conclusively, 2-[F-18]FPhe is a promising PET probe that is now readily available using Cu-mediated radiofluorination under 'minimalist' or 'low base' conditions. The simplicity of the translation of the proposed procedures to automated synthesis modules allows a broad biological evaluation of 2-[F-18]FPhe. Notably, a novel protocol for the preparation of N-Boc protected amino acids from the respective Ni-Schiff base complexes was developed that avoided application of strongly acidic conditions

Alcohol-Supported Cu-Mediated F-18-Fluorination of Iodonium Salts under Minimalist Conditions

In the era of personalized precision medicine, positron emission tomography (PET) and related hybrid methods like PET/CT and PET/MRI gain recognition as indispensable tools of clinical diagnostics. A broader implementation of these imaging modalities in clinical routine is closely dependent on the increased availability of established and emerging PET-tracers, which in turn could be accessible by the development of simple, reliable, and efficient radiolabeling procedures. A further requirement is a cGMP production of imaging probes in automated synthesis modules. Herein, a novel protocol for the efficient preparation of F-18-labeled aromatics via Cu-mediated radiofluorination of (aryl)(mesityl) iodonium salts without the need of evaporation steps is described. Labeled aromatics were prepared in high radiochemical yields simply by heating of iodonium [F-18]fluorides with the Cu-mediator in methanolic DMF. The iodonium [F-18]fluorides were prepared by direct elution of F-18(-) from an anion exchange resin with solutions of the corresponding precursors in MeOH/DMF. The practicality of the novel method was confirmed by the racemization-free production of radiolabeled fluorophenylalanines, including hitherto unknown 3-[F-18]FPhe, in 22-69% isolated radiochemical yields as well as its direct implementation into a remote-controlled synthesis unit