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Department of Internal Medicine, Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor, Michigan
Correspondence: For correspondence or reprints contact: Timothy R. DeGrado, PhD, Duke University Medical Center, Radiology Dept., Box 3808, Durham, NC 27710.
ABSTRACT
Carbon-11-labeled meta-hydroxyephedrine (HED, N-methyl-metaraminol) is a catecholamine analog developed for the PET imaging of sympathetic nerve terminals of the heart. The retention mechanisms of this tracer and interactions with norepinephrine were investigated in isolated working rat hearts. Externally monitored time-activity curves showed a strong uptake process in control hearts (K1 = 2.66 ± 0.39 ml/g/min) and relatively slow monoexponential clearance rates (k2 = 0.011 ± 0.003 min –1). Comparative studies with the neuronal uptake inhibitor desipramine indicated little extraneuronal distribution and a strong dependence of clearance rate on neuronal reuptake of tracer. Norepinephrine (
10 nM) increased HED clearance rate without affecting initial uptake rates. This effect may be related to competitive inhibition of neuronal reuptake and/or accelerated neuronal release of HED. These results indicate that the uptake and retention of HED by the myocardium is highly specific to sympathetic nerve terminals. However, its retention in the myocardium is not directly related to neuronal processing of catecholamines (i.e., metabolism and vesicular turnover). Thus, important differences may exist in the physiologic information indicated by retention measurements of HED and radiolabeled catecholamines. The finding of increased clearance rates with NE in the perfusion medium recommends the consideration of potential effects of circulating and endogenous catecholamines on PET measurements of myocardial retention of HED, especially in subjects with elevated plasma catecholamines or high sympathetic tone.
FOOTNOTES
* Present address: Duke University Medical Center, Radiology Dept., Box 3808, Durham, NC 27710.
Present address: Indiana University Medical Center, Dept. of Radiology, 541 Clinical Dr., Indianapolis, IN 46202-5111.
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