Key result
Dopamine β-hydroxylase catalyzed the synthesis of (−)-6-[18F]FNE from 6-[18F]FDA with a Km of 0.87 mM and Vmax of 0.011 μmoles/unit/min, differing significantly from dopamine (p<0.05).
The stereospecific in vitro synthesis of (−)-6-[18F]FNE from 6-[18F]FDA using dopamine β-hydroxylase is feasible, providing a potential pathway to produce this radiotracer for PET imaging of cardiac sympathetic innervation.
Enzymatic 6-[18F]FNE synthesis is feasible; leaves open validation for cardiac sympathetic PET imaging.
The visualization and investigation of the sympathetic innervation of the heart with positron emission tomography (PET) has become a new and active area in nuclear cardiology. The radiofluorinated amine (−)-6-[18F]-fluoronorepinephrine ((−)-6-[18F]FNE) has been suggested as a potential radiotracer for imaging the sympathetic nervous system and providing kinetic information regarding the utilization of the native adrenergic neurotransmitter norepinephrine. In this study, it was found that (−)-6-[18F]FNE can be synthesized stereospecifically from 6-[18F]-fluorodopamine (6-[18F]FDA) under in vitro conditions through the catalytic action of the enzyme dopamine β-hydroxylase (DβH), which is responsible for the in vivo biosynthesis of endogenous norepinephrine from dopamine. The estimated Km and Vmax values for the enzymatic activity of DβH on 6-[18F]FDA and on dopamine were 0.87±0.07 mM, 0.011±0.001 μmoles/unit/min, and 1.4±0.3 mM, and 0.079±0.017 μmoles/unit/min respectively. The differences between the Km and Vmax values of the two substrates were both statistically significant at p<0.05. Provided that 6-[18F]FDA with a sufficiently high specific activity is available, results from this study suggests that the enzymatic conversion of 6-[18F]FDA into (−)-6-[18F]FNE by DβH may be used to synthesize (−)-6-[18F]FNE suitable for intravenous administration into humans. Furthermore, this study also opens up the possibility of exploiting the low substrate specificity of DβH for the synthesis of other 11C- or 18F-labeled biogenic phenylethanolamines in their natural enantiomeric form for PET studies.
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Lui et al. (1998) studied this question. 6-[18F]-fluorodopamine (6-[18F]FDA) vs. dopamine was evaluated on Km and Vmax values for enzymatic activity of DβH (p=<0.05). Dopamine β-hydroxylase catalyzed the synthesis of (−)-6-[18F]FNE from 6-[18F]FDA with a Km of 0.87 mM and Vmax of 0.011 μmoles/unit/min, differing significantly from dopamine (p<0.05).
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