Enzymatic synthesis of (-)-6-[18F]-Fluoronorepinephrine from 6- [18F]-Fluorodopamine by dopamine β-hydroxylase

Article abstract of DOI:10.1002/(SICI)1099-1344(199806)41:6<503::AID-JLCR107>3.0.CO;2-I

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 K(m) and V(max) 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 K(m) and V(max) 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.