Positron emission tomographic imaging of cardiac sympathetic innervation and function.
Sites of uptake, storage, and metabolism of [18F]fluorodopamine and excretion of [18F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [18F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [18F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.
Goldstein
D S
DS
Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Chang
P C
PC
Eisenhofer
G
G
Miletich
R
R
Finn
R
R
Bacher
J
J
Kirk
K L
KL
Bacharach
S
S
Kopin
I J
IJ
D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives; D005462:Fluorine Radioisotopes; D005728:Ganglia, Sympathetic / Q000502:physiology; D015171:Ganglionectomy; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006439:Hemodynamics / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D009647:Normetanephrine / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology; D014055:Tomography, Emission-Computed; D014294:Trimethaphan / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D005462:Fluorine Radioisotopes; D009647:Normetanephrine; D009599:Nitroprusside; C029253:6-fluorodopamine; D014294:Trimethaphan; D012110:Reserpine; D003891:Desipramine; D004298:Dopamine; D014439:Tyramine