Molecular imaging of cardiac sympathetic innervation by 11C-mHED and PET: From man to mouse?

Abstract

Dysfunction of the sympathetic nervous system underlies many cardiac diseases and can be assessed by molecular imaging using PET in humans. Small-animal PET should enable non-invasive quantitation of the sympathetic nervous system in mouse models of human disease. For mice, however, the radioactivity needed to give acceptable image quality may be associated with a mass of unlabeled compound sufficient to block the binding of radioligand to its target. The present study assesses the feasibility of using [N-methyl- 11C]meta-hydroxyephedrine (11C-mHED) to measure norepinephrine reuptake in humans, to determine cardiac innervation in mice. Methods: Anesthetized mice were placed in a small-animal PET scanner. 11C-mHED (containing 18% precursor metaraminol) was injected via a tail vein into each animal simultaneously. Fifteen minutes later, animals were injected with saline or metaraminol which competes with mHED for norepinephrine reuptake. 18F-FDG was injected at 60 min to identify heart regions. After reconstruction of the list-mode data, radioactivity in myocardial regions was computed using in-house software, and time-activity curves were plotted. Results: Hearts were clearly visualized after injection of 11C-mHED. Injection of metaraminol at doses less than 50 nmol•kg-1 had no effect, whereas doses greater than 100 nmol•kg-1 caused a dose-dependent loss of specifically bound radioactivity. Conclusion: 11C-mHED was successfully used to visualize and assess myocardial innervation in mice. Uptake of 11C-mHED is displaceable by the false transmitter metaraminol. The total molar dose of metaraminol and 11C-mHED must be considered in the analysis of PET data. Copyright © 2010 by the Society of Nuclear Medicine, Inc.