Enzymatic synthesis of no-carrier-added 6-[18F]fluoro-L-dopa with beta-tyrosinase.
An enzymatic synthesis of nca 6-[18F]fluoro-L-dopa has been developed. The process consists of a chemical synthesis of 4-[18F]fluorocatechol and its enzymatic reaction with beta-tyrosinase. The 4-[18F]fluorocatechol was prepared by nucleophilic aromatic substitution of the NO2 group on 6-nitroveratoraldehyde with [K/222]+18F-, followed by decarbonylation with tris(triphenylphosphine) rhodium(I) chloride and hydrolysis with hydroiodic acid. By C18 Sep-Pak purification, 4-[18F]fluorocatechol was obtained in ethanol with a radiochemical yield of 9.2%. An enzymatic reaction of 4-[18F]fluorocatechol, ammonium and pyruvate catalyzed by beta-tyrosinase in an ethanolic Tris-HCl buffer (pH 9.0) containing ascorbate gave within 5 min 6-[18F]fluoro-L-dopa with an approximate radiochemical yield of 60% without any isomers. The deproteinized reaction mixture was applied to a preparative reverse phase column, and the radiochemically and enantiomerically pure 6-[18F]fluoro-L-dopa was obtained with a radiochemical yield of 2.0% based on [18F]F- (decay-corrected). The synthesis time was 150 min from the EOB and the specific activity was > 200 GBq/micromol.
Kaneko
S
S
Positon Medical Center, Tokyo Metropolitan Institute of Gerontology, Naka-cho Itabashi, Japan.
Ishiwata
K
K
Hatano
K
K
Omura
H
H
Ito
K
K
Senda
M
M
D002851:Chromatography, High Pressure Liquid; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D007536:Isomerism; D007700:Kinetics; D015394:Molecular Structure; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D014447:Tyrosine Phenol-Lyase
D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D014447:Tyrosine Phenol-Lyase