title: Fate of tritiated 6-fluorodopamine in rats: a false neurotransmitter for positron emission tomographic imaging of sympathetic innervation and function.
abstract: 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)
authors.affiliation: Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
authors.forename: P C
authors.initials: PC
authors.lastname: Chang
authors.forename: K
authors.initials: K
authors.lastname: Szemeredi
authors.forename: E
authors.initials: E
authors.lastname: Grossman
authors.forename: I J
authors.initials: IJ
authors.lastname: Kopin
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005089:Exocytosis; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009647:Normetanephrine / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014316:Tritium; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D009647:Normetanephrine; D014316:Tritium; D009599:Nitroprusside; D015016:Yohimbine; C029253:6-fluorodopamine; D012110:Reserpine; D003891:Desipramine; D004298:Dopamine