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

Journal of Nuclear Medicine

Klaus Kopka¹  Otmar Schober¹  Michael Schäfers¹  Stefan Wagner¹  Marilyn P. Law¹  Klaus Schäfers¹ 

关键词: ¹¹C-meta-hydroxyephedrine;    norepinephrine reuptake;    sympathetic innervation;    cardiac imaging;    small-animal PET;   

DOI  :  10.2967/jnumed.110.074997

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 noninvasive 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.

【 授权许可】

Unknown