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 http://jnm.snmjournals.org/cgi/content/abstract/46/11/1775

Cardiac and Extracardiac Sympathetic Denervation in Parkinson's Disease with
Orthostatic Hypotension and in Pure Autonomic Failure

Dnyanesh N. Tipre, MPharm, PhD and David S. Goldstein, MD, PhD

Clinical Neurocardiology Section, National Institute of Neurological Disorders
and Stroke, National Institutes of Health, Bethesda, Maryland


The uptake of 6-18F-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 6-18F-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 6-18F-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 6-18F-fluorodopamine scanning of the head, thorax, and
abdomen, with or without treatment with desipramine to block sympathoneural
uptake of catecholamines. 13N-Ammonia scanning was used to address possible
group differences in 6-18F-fluorodopamine delivery by blood perfusion.
Results: Desipramine treatment was associated with decreased
6-18F-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
6-18F-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
13N-ammonia-derived radioactivity. Conclusion: 6-18F-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.



Key Words: fluorodopamine * ammonia * pure autonomic failure * Parkinson's
disease * PET

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