Positron emission tomographic imaging of cardiac sympathetic Innervation using 6-[18F]Fluorodopamine: Initial findings in humans

David S. Goldstein, Graeme Eisenhofer, Bonnie B. Dunn, Ines Armando, Jacques Lenders, Ehud Grossman, Courtney Holmes, Kenneth L. Kirk, Stephen Bacharach, Richard Adams, Peter Herscovitch, Irwin J. Kopin

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives. This study evaluated the safety, efficacy and validity of 6-[18F]fluorodopamine positron emission tomographic scanning of cardiac sympathetic innervation and function in humans. Methods. Positron emission tomographic (PET) scans, arterial blood and urine were obtained after a 3-min intravenous infusion of 6-[18F]fluorodopamine (1 to 4 mCi, 188 to 809 mCi/mmol) in healthy volunteers, with or without pretreatment with oral desipramine to inhibit neuronal uptake of catecholamines. Results. 6-[18F]Fluorodopamine PET scanning visualized the left ventricular myocardium. Blood pressure increased slightly and transiently. The estimated absorbed radiation dose to the main target organ, the wall of the urinary bladder, was 0.8 to 1.0 rad/mCi of injected 6-[18F]fluorodopamine. By 24 h after the injection, the main 6F-compound in urine was 6F-vanillylmandelic acid, a metabolite of 6F-norepinephrine. Desipramine attenuated accumulation of myocardial 6-[18F]fluorodopamine-derived radioactivity and plasma 6Fdihydroxyphenylacetic acid. Conclusions. 6-[18F]Fluorodopamine produces negligible hemodynamic effects and acceptable radiation exposure at doses that visualize the left ventricular myocardium. Sympathetic nerves take up 6-[18F]fluorodopamine, which is translocated from the axoplasm into storage vesicles, where is it beta-hydroxylated to the fluorinated analogue of the sympathetic neurotransmitter norepinephrine. Therefore, the basis for visualization of myocardium after 6-[18F]fluorodopamine injection in humans is radiolabeling by 6-[18F]fluorodopamine and 6-[18F]fluoronorepinephrine of vesicles in sympathetic terminals. 6-[18F]Fluorodopamine PET scanning provides a novel means for assessing sympathetic innervation and function noninvasively in the human heart.

Original languageEnglish
Pages (from-to)1961-1971
Number of pages11
JournalJournal of the American College of Cardiology
Volume22
Issue number7
DOIs
StatePublished - Dec 1993
Externally publishedYes

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