HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raffel, D. M. Articles by Jung, Y.-W. Search for Related Content PubMed PubMed Citation Articles by Raffel, D. M. Articles by Jung, Y.-W.

Dependence of Cardiac ¹¹C-meta-Hydroxyephedrine Retention on Norepinephrine Transporter Density

Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan

Correspondence: For correspondence or reprints contact: David M. Raffel, PhD, Division of Nuclear Medicine, Department of Radiology, 3480 Kresge III Bldg., University of Michigan Medical School, Ann Arbor, MI 48109-0552. E-mail: raffel{at}umich.edu

The norepinephrine analog ¹¹C-meta-hydroxyephedrine (HED) is used with PET to map the regional distribution of cardiac sympathetic neurons. HED is rapidly transported into sympathetic neurons by the norepinephrine transporter (NET) and stored in vesicles. Although much is known about the neuronal mechanisms of HED uptake and retention, there is little information about the functional relationship between HED retention and cardiac sympathetic nerve density. The goal of this study was to characterize the dependence of HED retention on nerve density in rats with graded levels of cardiac denervation induced chemically with the neurotoxin 6-hydroxydopamine (6-OHDA). Methods: Thirty male Sprague–Dawley rats were divided into 6 groups, and each group was administered a different dose of 6-OHDA: 0 (controls), 7, 11, 15, 22, and 100 mg/kg intraperitoneally. One day after 6-OHDA injection, HED (3.7–8.3 MBq) was injected intravenously into each animal and HED concentrations in heart and blood at 30 min after injection were determined. Heart tissues were frozen and later processed by tissue homogenization and differential centrifugation into a membrane preparation for in vitro measurement of cardiac NET density. A saturation binding assay using ³H-mazindol as the radioligand was used to measure NET density (maximum number of binding sites [B_max], fmol/mg protein) for each heart. Results: In control animals, NET B_max was 388 ± 23 fmol/mg protein and HED heart uptake (HU) at 30 min was 2.89% ± 0.35 %ID/g (%ID/g is percentage injected dose per gram tissue). The highest 6-OHDA dose of 100 mg/kg caused severe cardiac denervation, decreasing both NET B_max and HED HU to 8% of their control values. Comparing values for all doses of 6-OHDA, HED retention had a strong linear correlation with NET density: HU = 0.0077B_max –0.028, r² = 0.95. Conclusion: HED retention is linearly dependent on NET density in rat hearts that have been chemically denervated with 6-OHDA, suggesting that HED retention is a good surrogate measure of NET density in the rat heart. This finding is discussed in relation to clinical observations of the dependence of HED retention on cardiac nerve density in human subjects using PET.

Key Words: sympathetic nervous system • meta-hydroxyephedrine • 6-hydroxydopamine • norepinephrine transporter • PET

Related articles in JNM:

This Month in JNM

JNM 2006 47: 9a-10a. [Full Text]  

This article has been cited by other articles:

				J. T. Thackeray, R. S. Beanlands, and J. N. DaSilva Presence of Specific 11C-meta-Hydroxyephedrine Retention in Heart, Lung, Pancreas, and Brown Adipose Tissue J. Nucl. Med., October 1, 2007; 48(10): 1733 - 1740. [Abstract] [Full Text] [PDF]