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


CONCLUSIONS
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.
Tipre
Dnyanesh N
DN
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. dnyanesht@yahoo.com
Goldstein
David S
DS
D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000000981:diagnostic imaging* / Q000187:drug effects; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging*; D003891:Desipramine; D004298:Dopamine / Q000031:analogs & derivatives*; D005462:Fluorine Radioisotopes; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000294:innervation; D006801:Humans; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012791:Shy-Drager Syndrome / Q000139:chemically induced / Q000000981:diagnostic imaging*; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000187:drug effects
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C029253:6-fluorodopamine; D003891:Desipramine; D004298:Dopamine