Fate of tritiated 6-fluorodopamine in rats: A false neurotransmitter for positron emission tomographic imaging of sympathetic innervation and function

In evaluating positron-emitting analogs of dopamine (DA) as imaging agents for visualizing tissue sympathetic innervation and function, we assessed the metabolic fate of systemically injected [³H]-6- fluorodopamine ([³H]-6F-DA) in plasma, in sympathetically innervated tissues (left ventricle, spleen and salivary glands) and in excretory organs (liver and kidney) of rats. By 5 min after intravenous bolus injection of a physiologically inactive amount (450 ng, 10 μCi) of [³H]-6F-DA, ³H was concentrated in all the organs compared with that in blood or plasma. In the sympathetically innervated organs, most of the radioactivity ws in [³H]-6F-DA and [³H]-6-fluoronorepinephrine ([³H]-6F-NE), whereas in the blood, plasma and excretory organs most of the radioactivity was in noncatechol compounds such as O-methylated and conjugated metabolites. In sympathetically innervated organs, tissue/blood ratios exceeded 1.0 at all time points between 5 and 120 min after injection of [³H]-6F-DA and increased progressively (from 8 to 60 in myocardium), whereas the tissue/blood ratios in the kidney and liver increased by less than 2-fold during this interval. In all the studied tissues, the proportion of total tissue ³H that was due to [³H]F-NE increased progressively while that due to [³H]F-DA declined, consistent with conversion of [³H]F-DA to [³H]F-NE in vesicles in sympathetic nerve endings. Patterns of tissue and plasma ³H-labeled compounds after treatment with desipramine, reserpine, yohimbine, normetanephrine or nitroprusside were consistent with the view that in sympathetically innervated organs [³H]-6F-DA is removed by neuronal uptake, translocated into axoplasmic vesicles and converted to [³H]-6F-NE and released by leakage and by exocytosis during sympathetic activity. The results suggest that after injection of [¹⁸F]F-DA, visualization of tissue sympathetic innervation and aspects of sympathetic function should be feasible by positron emission tomography.