Abstract 16604: Discrepant Uptake of the Sympathetic Nerve Imaging Tracers Hydroxyephedrine (HED) and Metaiodobenzylguanidine (MIBG) in Rat Hearts
Aim: Different established catecholamine analogues are available for clinical cardiac sympathetic nerve PET/SPECT imaging, including 11C Hydroxyephedrine (HED) and 123I/131I Metaiodobenzylguanidine (MIBG). In contrast to humans, rat hearts are known to have a high fraction of non-neural catecholamine uptake-2. Hence, we aimed to determine the neural uptake contribution of these tracers in rats.
Methods: Healthy Wistar rats (n=22) were studied using following pretreatments: (1) uptake-1 blockade with Desipramine 2mg/kg, (2) both uptake-1 and -2 blockade with Phenoxybenzamine 50mg/kg, or (3) control with saline. The respective tracer, HED or MIBG, was injected 10 min after pretreatment, and rats were sacrificed 10 min after tracer injection. Heart to blood tissue count ratio (H/B ratio) was obtained using a gamma counter. To determine the regional distribution of tracer uptake, dual tracer autoradiography was performed with HED and 131I MIBG in a rat model of chronic infarction (n=6). Local tracer distributions were then compared with histology.
Results: The H/B ratio in the control hearts were 34.4±1.7 and 25.5±2.1 for HED and MIBG, respectively. Neural uptake-1 blockade lead to a significant decrease (p<0.0001) in HED (3.2±0.5), while there was no change in MIBG (25.5±6.4, p=n.s.). On the other hand, both uptake-1 and -2 blockade lead to a significant decrease (p<0.0001) in both HED and MIBG (3.5±0.02, 4.3±0.7). Regional MIBG distribution in infarction model hearts demonstrated that the MIBG uptake defect closely matched the scar area determined by histology (3.8±2.3% (MIBG defect) vs. 4.0±2.4% (scar)), however the HED uptake defect (9.1±2.2%, p<0.001) clearly exceeded the scar area.
Conclusion: In rat hearts, HED uptake showed high specificity to neural uptake-1. On the other hand, MIBG demonstrated distinct characters of regional tracer distribution and uptake mechanism with significant contribution of non-neural uptake-2.
- © 2011 by American Heart Association, Inc.