Metabolic fate of the sympathoneural imaging agent 6-[18F]fluorodopamine in humans.
We examined the metabolism of 6-[18F]fluorodopamine, by assaying arterial plasma concentrations of radioactivity, 6-[18F]fluorodopamine, and 6-[18F]fluorodopamine metabolites in untreated subjects or subjects given desipramine to block neuronal uptake of catecholamines or tyramine to displace vesicular amines. After the 3-min 6-[18F]fluorodopamine infusion, plasma 6-[18F]fluorodopamine levels declined precipitously, total radioactivity declining slowly. After 30 min, the main identified metabolite was 6-[18F]fluorodopamine-sulfate. Desipramine attenuated the rapid increase in plasma 6-[18F]fluorodihydroxyphenylacetic acid levels, and tyramine briefly increased 6-[18F]fluorodopamine levels. Neither drug affected 6-[18F]fluorodopamine-sulfate levels. The results indicate that soon after 6-[18F]fluorodopamine infusion, plasma radioactivity corresponds mainly to 6-[18F]fluorodopamine metabolites; that sympathetic nerves rapidly remove 6-[18F]fluorodopamine, which then undergoes oxidative deamination in the neuronal cytoplasm and sequestration in sympathetic vesicles; and that sulfoconjugation of [18F]fluorodopamine occurs extraneuronally.
Goldstein
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DS
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1424, USA. daveg@box-d.nih.gov
Holmes
C
C
D000284:Administration, Oral; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D002853:Chromatography, Liquid; D003891:Desipramine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000008:administration & dosage / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods; D014439:Tyramine / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D002395:Catecholamines; D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D003891:Desipramine; D014439:Tyramine