An approach to the asymmetric synthesis of 18F-labeled analog of L-threo-3,4-dihydroxyphenylserine (6-L-threo-[18F]FDOPS) - a new radiotracer for visualization of norepinephrine transporters by positron emission tomography

An asymmetric synthesis method has been suggested as a feasible approach for the preparation of fluorine-18-labeled (T-1/2 110 min) analog of L-threo-3,4-dihydroxyphenylserine, i.e., 6-L-threo- [F-18]FDOPS ((2S,3R)-2-amino-3-(2-[F-18]fluoro-4,5-dihydroxypheny1)-3-hydroxypropionic acid), a new radiotracer for the evluation of norepinephrine transporters by positron emission tomography (PET). The approach is based on the condensation reaction of 2-[F-18]fluoro-4,5-bis(methoxymethoxy)benzaldehyde with a chiral nickel(II) complex and glycine (Ni-(R)-BPB-Gly) with subsequent removal of protection from hydroxy groups by acid hydrolysis. The radiochemical synthesis includes three steps and can be easily implemented into modern automated modules for the synthesis of radiopharmaceutical agents for PET.