Synthesis of high specific activity (+)- and (-)-6-[18F]fluoronorepinephrine via the nucleophilic aromatic substitution reaction.
The first example of a no-carrier-added 18F-labeled catecholamine, 6-[18F]fluoronorepinephrine (6-[18F]FNE), has been synthesized via nucleophilic aromatic substitution. The racemic mixture was resolved on a chiral HPLC column to obtain pure samples of (-)-6-[18F]FNE and (+)6-[18F]FNE. Radiochemical yields of 20% at the end of bombardment (EOB) for the racemic mixture (synthesis time 93 min), 6% for each enantiomer (synthesis time 128 min) with a specific activity of 2-5 Ci/mumol at EOB were obtained. Chiral HPLC peak assignment for the resolved enantiomers was achieved by using two independent methods: polarimetric determination and reaction with dopamine beta-hydroxylase. Positron emission tomography (PET) studies with racemic 6-[18F]FNE show high uptake and retention in the baboon heart. This work demonstrates that nucleophilic aromatic substitution by [18F]fluoride ion is applicable to systems having electron-rich aromatic rings, leading to high specific activity radiopharmaceuticals. Furthermore, the suitably protected dihydroxynitrobenzaldehyde 1 may serve as a useful synthetic precursor for the radiosynthesis of other complex 18F-labeled radiotracers.
Ding
Y S
YS
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973.
Fowler
J S
JS
Gatley
S J
SJ
Dewey
S L
SL
Wolf
A P
AP
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005462:Fluorine Radioisotopes; D006321:Heart / Q000000981:diagnostic imaging; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D010215:Papio; D013237:Stereoisomerism; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; C024884:6-fluoronorepinephrine; D009638:Norepinephrine