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 microCi) 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 was 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.(ABSTRACT TRUNCATED AT 250 WORDS)