Cardiac and extracardiac sympathetic denervation in Parkinson's disease with orthostatic hypotension and in pure autonomic failure.

Abstract

UNLABELLED:

The uptake of 6-(18)F-fluorodopamine by cardiac noradrenergic nerves enables visualization of the sympathetic innervation of the left ventricular myocardium by PET. Patients with Parkinson's disease (PD) and orthostatic hypotension (OH) (PD+OH) or with pure autonomic failure (PAF) have markedly decreased myocardial 6-(18)F-fluorodopamine-derived radioactivity, consistent with cardiac sympathetic denervation, a phenomenon that neurochemical, neuropharmacologic, and, most recently, postmortem neuropathologic studies have confirmed. In this study, we examined whether 6-(18)F-fluorodopamine can visualize sympathetic innervation in extracardiac organs and, if so, whether patients with PD+OH or PAF have neuroimaging evidence of extracardiac noradrenergic denervation.

METHODS:

To validate the method, healthy volunteers underwent 6-(18)F-fluorodopamine scanning of the head, thorax, and abdomen, with or without treatment with desipramine to block sympathoneural uptake of catecholamines. (13)N-Ammonia scanning was used to address possible group differences in 6-(18)F-fluorodopamine delivery by blood perfusion.

RESULTS:

Desipramine treatment was associated with decreased 6-(18)F-fluorodopamine-derived radioactivity in the heart, renal cortex, and thyroid gland but not in the liver, spleen, renal pelvis, or salivary glands. Both the PD+OH group and the PAF group had decreased 6-(18)F-fluorodopamine-derived radioactivity in the heart (P < 0.0001) and renal cortex (P = 0.02 and P = 0.005, respectively). The PD+OH group also had decreased radioactivity in the thyroid gland (P = 0.01). Neither group had decreased radioactivity in the other organs, after correction for (13)N-ammonia-derived radioactivity.

CONCLUSION:

6-(18)F-Fluorodopamine scanning visualizes sympathetic innervation in the heart, renal cortex, and thyroid gland. Both PD+OH and PAF involve decreased noradrenergic innervation that is most prominent in the heart but is also detectable in extracardiac organs.

• Authors: Dnyanesh N Tipre, David S Goldstein
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 46 Issue 11 Pg. 1775-81 (Nov 2005) ISSN: 0161-5505 [Print] United States
• PMID: 16269589 (Publication Type: Controlled Clinical Trial, Journal Article)

Chemical References

• Fluorine Radioisotopes
• Radiopharmaceuticals
• 6-fluorodopamine
• Desipramine
• Dopamine

Topics

• Adult
• Aged
• Autonomic Nervous System (diagnostic imaging, drug effects)
• Autonomic Nervous System Diseases (chemically induced, diagnostic imaging)
• Desipramine
• Dopamine (analogs & derivatives)
• Fluorine Radioisotopes
• Heart Ventricles (diagnostic imaging, drug effects, innervation)
• Humans
• Middle Aged
• Parkinsonian Disorders (chemically induced, diagnostic imaging)
• Radionuclide Imaging
• Radiopharmaceuticals
• Reproducibility of Results
• Sensitivity and Specificity
• Shy-Drager Syndrome (chemically induced, diagnostic imaging)
• Sympathetic Nervous System (diagnostic imaging, drug effects)