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

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

doi:10.1016/0735-1097(93)90786-z

Cited by 93 publications

(55 citation statements)

References 14 publications

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“…infusion of trimethaphan to block ganglionic neurotransmission (Goldstein et al, , 1993(Goldstein et al, , 1997b. The results, and similarities to those during ganglion blockade in other studies, lead us to propose early neurotoxic effects of MPTP at the level of preganglionic or ganglionic neurotransmission, resulting in decreased exocytotic release of norepinephrine from intact cardiac sympathetic terminals.…”

Section: Discussionsupporting

confidence: 50%

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Sympathetic Innervation in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Primate Model of Parkinson's Disease

Goldstein

Li²,

Holmes³

et al. 2003

J Pharmacol Exp Ther

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Cardiac sympathetic denervation occurs commonly in Parkinson's disease. This study explored whether analogous denervation occurs in primates with Parkinsonism from systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 6-[18 F]Fluorodopamine positron emission tomographic scanning and plasma levels of catecholamines and their deaminated metabolites were used to assess sympathetic and adrenomedullary function in rhesus monkeys, in the untreated state (n ϭ 3), 2 weeks after a series of four MPTP injections, before establishment of Parkinsonism (acute phase, n ϭ 1); a month later, after four more MPTP doses, associated with severe Parkinsonism (subacute phase, n ϭ 1); or more than 2 years from the last dose (remote phase, n ϭ 3), with persistent severe Parkinsonism. A positive control received i.v. 6-hydroxydopamine 1 week before 6-[18 F]fluorodopamine scanning. Acute MPTP treatment increased cardiac 6-[18 F]fluorodopamine-derived radioactivity, whereas 6-hydroxydopamine markedly decreased cardiac radioactivity, despite similarly low plasma levels of catecholamines and metabolites after either treatment. Subacutely, plasma catecholamines remained decreased, but now with myocardial 6-[18 F]fluorodopamine-derived radioactivity also decreased. Remotely, MPTP-treated monkeys had lower plasma catecholamines and higher myocardial 6-[18 F]fluorodopamine-derived radioactivity than did untreated animals. The results indicate that in nonhuman primates, systemic MPTP administration produces multiphasic effects on peripheral catecholamine systems, with nearly complete recovery by 2 years. MPTP-and 6-hydroxydopamine-induced changes differ markedly, probably from ganglionic or preganglionic neurotoxicity with the former and more severe cardiac sympathetic neurotoxicity with the latter. Because of multiphasic sympathetic and adrenomedullary effects, without cardioselective sympathetic denervation at any time, the primate MPTP model does not mimic the changes in peripheral catecholamine systems that characterize the human disease.Parkinson's disease features cardiac sympathetic denervation, as evidenced by decreased myocardial concentrations of radioactivity after administration of the sympathoneural imaging agents 123 I-metaiodobenzylguanidine (Satoh et al

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Section: Discussionsupporting

confidence: 50%

“…The pattern in this subacute phase bore a striking resemblance to that in healthy volunteers and in anesthetized dogs after treatment with desipramine to block the cell membrane norepinephrine transporter (Goldstein et al, , 1993(Goldstein et al, , 1997b. Desipramine exerts two major effects on sympathetic neuroeffector function.…”

Section: Discussionmentioning

confidence: 90%

Sympathetic Innervation in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Primate Model of Parkinson's Disease

Goldstein

Li²,

Holmes³

et al. 2003

J Pharmacol Exp Ther

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“…In both cases, repeated imaging studies after surgical resection of pheochromocytoma showed that BAT had disappeared, suggesting that perhaps the lack of uptake on follow-up was due to resolution of the sympathetic stimuli. We postulate that the mechanism of uptake of 18 F-F-DA seen in BAT may be similar to that of 123 I-MIBG, given that 18 F-F-DA and 123 I-MIBG have similar mechanisms of uptake (19,(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Brown Fat Imaging with 18F-6-Fluorodopamine PET/CT, 18F-FDG PET/CT, and 123I-MIBG SPECT: A Study of Patients Being Evaluated for Pheochromocytoma

Hadi¹,

Chen²,

Whatley³

et al. 2007

Journal of Nuclear Medicine

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“…Cardiac sympathetic nerves take up 123 Imetaiodobenzylguanidine ( 123 I-MIBG) and 6-[ 18 F]fluorodopamine, which radiolabel the vesicles in the terminals (11,12). This allows visualization of the sympathetic innervation of the heart by scintigraphy or single-photon emission computed tomography after injection of 123 I-MIBG (13) and by positron emission tomography (PET) after injection of 6-[ 18 F]fluorodopamine (14). This visualization is independent of adrenoceptor binding; rather, it depends on active transport of the radioactive drug by the uptake-1 process, followed by vesicular sequestration.…”

Section: Chronic Autonomic Failurementioning

confidence: 99%

Dysautonomias: Clinical Disorders of the Autonomic Nervous System

Goldstein

Robertson²,

Esler³

et al. 2002

Ann Intern Med

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The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The changes range from transient, occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases; from disorders in which altered autonomic function plays a primary pathophysiologic role to disorders in which it worsens an independent pathologic state; and from mechanistically straightforward to mysterious and controversial entities. In chronic autonomic failure (pure autonomic failure, multiple system atrophy, or autonomic failure in Parkinson disease), orthostatic hypotension reflects sympathetic neurocirculatory failure from sympathetic denervation or deranged reflexive regulation of sympathetic outflows. Chronic orthostatic intolerance associated with postural tachycardia can arise from cardiac sympathetic activation after "patchy" autonomic impairment or blood volume depletion or, as highlighted in this discussion, from a primary abnormality that augments delivery of the sympathetic neurotransmitter norepinephrine to its receptors in the heart. Increased sympathetic nerve traffic to the heart and kidneys seems to occur as essential hypertension develops. Acute panic can evoke coronary spasm that is associated with sympathoneural and adrenomedullary excitation. In congestive heart failure, compensatory cardiac sympathetic activation may chronically worsen myocardial function, which rationalizes treatment with ␤-adrenoceptor blockers. A high frequency of positive results on tilt-table testing has confirmed an association between the chronic fatigue syndrome and orthostatic intolerance; however, treatment with the salt-retaining steroid fludrocortisone, which is usually beneficial in primary chronic autonomic failure, does not seem to be beneficial in the chronic fatigue syndrome. Dysautonomias are an important subject in clinical neurocardiology. The notion that the sympathetic nervous system coordinates body functions probably originated with the second-century Greek physician Galen, who taught that nerves were hollow tubes distributing "animal spirits" in the body, thereby fostering concerted action, or "sympathy," of the organs. In 1552, Bartolomeo Eustachius first depicted the sympathetic nerves and the adrenal glands. Winslow reintroduced the sympathetic nervous system in 1732 to describe the chains of ganglia and nerves connected to the thoracic and lumbar spinal cord.The functions of these structures remained unknown until the 19th century, when Bernard and others first reported the effects of sympathetic nerve stimulation. In 1895, Oliver and Schäfer described the potent cardiovascular stimulatory effects of adrenal extracts. Soon afterward-almost exactly a century ago-Abel and Takamine identified epinephrine ("adrenaline" in British and European countries) as the active principle of the adrenal gland.Also in the late 19th century, Langley coined the term autonomic nervous system to denote the portion of the nervous system largely responsible for involuntary, unc...

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

Cited by 93 publications

References 14 publications

Sympathetic Innervation in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Primate Model of Parkinson's Disease

Sympathetic Innervation in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Primate Model of Parkinson's Disease

Brown Fat Imaging with 18F-6-Fluorodopamine PET/CT, 18F-FDG PET/CT, and 123I-MIBG SPECT: A Study of Patients Being Evaluated for Pheochromocytoma

Dysautonomias: Clinical Disorders of the Autonomic Nervous System

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