Molecular Imaging of Cardiac Sympathetic Innervation by 11C-mHED and PET: From Man to Mouse?

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-C-11]metahydroxyephedrine (C-11-mHED) to measure norepinephrine reuptake in humans, to determine cardiac innervation in mice. Methods: Anesthetized mice were placed in a small-animal PET scanner. C-11-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. F-18-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 C-11-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: C-11-mHED was successfully used to visualize and assess myocardial innervation in mice. Uptake of C-11-mHED is displaceable by the false transmitter metaraminol. The total molar dose of metaraminol and C-11-mHED must be considered in the analysis of PET data.