Enzymatic synthesis of (−)‐6‐[18F]‐fluoronorepinephrine from 6‐[18F]‐fluorodopamine by dopamine β‐hydroxylase

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. © 1998 John Wiley & Sons, Ltd.