Methods for the synthesis of fluorine-18-labeled aromatic amino acids, radiotracers for positron emission tomography (PET)

Nucleophilic Synthesis of 6-l-[18F]FDOPA. Is Copper-Mediated Radiofluorination the Answer?

“…Using various achiral substrate-PTC pairs for the key alkylation step, this approach was found to be suitable for generating 6- l -[ 18 F]FDOPA in moderate to high radiochemical yields, enantiomeric purity of 98% and A m as high as 0.75 TBq/µmol [ 47 ]. The details of this methodology can be found in the original publications [ 45 , 46 , 47 , 48 ] and summarized in the recent reviews of the synthesis of 6- l -[ 18 F]FDOPA [ 33 , 35 ]. In general, the PTC-based multi-step approaches have also suffered from the problem of being difficult to implement in commercially available synthetic modules existing.…”

“…Recent developments in radiofluorination methodologies including traditional multi-step nucleophilic aromatic substitution (S N Ar) reactions and novel “late-stage” transition metal-mediated approaches offer new routes for the introduction of fluorine-18 into non-activated arenes (and thus to the labeling of ring-fluorinated aromatic amino acids). Although advancements made in the preparation of 6- l -[ 18 F]FDOPA have been the subject of several reviews published between 2014 and 2017 [ 33 , 34 , 35 , 36 ], this field has progressed tremendously since. It can be illustrated by an excellent review paper by Scott and co-workers, demonstrating the advances achieved within last 5 years in the field of labeling various arenes via Cu-mediated radiofluorinations [ 37 ].…”