title: Positron emission imaging of cardiac sympathetic innervation and function using 18F-6-fluorodopamine: effects of chemical sympathectomy by 6-hydroxydopamine.
abstract: Hypotheses concerning the pathophysiology of hypertension, cardiac failure and other cardiovascular disorders have imputed abnormal cardiac sympathoneural activity. Here we describe a technique to examine cardiac sympathetic innervation and function using positron emission tomographic (PET) scanning after systemic intravenous injection of 18F-6-fluorodopamine, and the effects of chemical sympathectomy by the neurotoxin, 6-hydroxydopamine (6-OHDA). Uptake of 18F-6-fluorodopamine by the heart of anesthetized dogs resulted in striking delineation of the left ventricular myocardium. Myocardial radioactivity declined bi-exponentially, with a half-life of approximately 2 h during the longer phase. In 6-OHDA-treated animals, the ventricular myocardium was barely distinguishable from the chamber; myocardial radioactivity declined rapidly and was virtually absent within 30 min after injection of 18F-6-fluorodopamine. The rates of decline in myocardial radioactivity in dogs treated with 6-OHDA were similar to those in dogs treated with reserpine, but the mechanisms of sympatholysis by these drugs were distinguished by arterial plasma levels of 6-fluorodihydroxyphenylacetic acid (6-FDOPAC). Plasma 6-FDOPAC levels were diminished in 6-OHDA-treated dogs and elevated in reserpinized dogs. The results confirm that, after injection of 18F-6-fluorodopamine, cardiac sympathetic nerve endings are radiolabeled, allowing visualization of sites of sympathetic innervation. Combined assessments of PET time-activity curves and plasma levels of metabolites of 18F-6-fluorodopamine constitute a new, potentially clinically applicable means by which to examine cardiac sympathetic function.
authors.affiliation: Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892.
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: E
authors.initials: E
authors.lastname: Grossman
authors.forename: M
authors.initials: M
authors.lastname: Tamrat
authors.forename: P C
authors.initials: PC
authors.lastname: Chang
authors.forename: G
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: J
authors.initials: J
authors.lastname: Bacher
authors.forename: K L
authors.initials: KL
authors.lastname: Kirk
authors.forename: S
authors.initials: S
authors.lastname: Bacharach
authors.forename: I J
authors.initials: IJ
authors.lastname: Kopin
mesh_terms: D000818:Animals; D002396:Catechols / Q000097:blood; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives*; D005462:Fluorine Radioisotopes; D006207:Half-Life; D006321:Heart / Q000294:innervation*; D006439:Hemodynamics; D006892:Hydroxydopamines; D008991:Monitoring, Physiologic; D009498:Neurotoxins; D016627:Oxidopamine; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000502:physiology; D014055:Tomography, Emission-Computed
chemical_list: D002396:Catechols; D005462:Fluorine Radioisotopes; D006892:Hydroxydopamines; D009498:Neurotoxins; C029253:6-fluorodopamine; D016627:Oxidopamine; D004298:Dopamine