Quantitation of cardiac sympathetic innervation in rabbits using ¹¹C-hydroxyephedrine PET: Relation to ¹²³I-MIBG uptake

Purpose: Although ¹¹C-hydroxyephedrine (¹¹C-HED) PET is used to map cardiac sympathetic innervation, no studies have shown the feasibility of quantitation of ¹¹C-HED PET in small- to medium-sized animals. Furthermore, its relation to ¹²³I-MIBG uptake, the most widely used sympathetic nervous tracer, is unknown. The aims of this study were to establish in vivo sympathetic nerve imaging in rabbits using ¹¹C-HED PET, and to compare the retention of ¹¹C-HED with that of ¹²³I-MIBG. Methods: Twelve rabbits were assigned to three groups; control (n=4), chemical denervation by 6-hydroxydopamine (6-OHDA) (n=4) and reserpine treated to inhibit vesicular uptake (n=4). After simultaneous injection of ¹¹C-HED and ¹²³I-MIBG, all animals underwent dynamic ¹¹C-HED PET for 40 min with arterial blood sampling. The ¹¹C-HED retention fraction and normalised ¹¹C-HED activity measured by tissue sampling were compared with those measured by PET. Results: Both the ¹¹C-HED retention fraction and the normalised ¹¹C-HED activity measured by PET correlated closely with those measured by tissue sampling (R=0.96027, p<0.001 and R=0.97282, p<0.001, respectively). Inhibition study by 6-OHDA resulted in a significant reduction in retention (90%) for both ¹¹C-HED and ¹²³I-MIBG. Reserpine pretreatment reduced ¹¹C-HED retention by 50%, but did not reduce ¹²³I-MIBG retention at 40 min after injection. Conclusion: Non-invasive quantitation of cardiac sympathetic innervation using ¹¹C-HED PET is feasible and gives reliable estimates of cardiac sympathetic innervation in rabbits. Additionally, although both ¹¹C-HED and ¹²³I-MIBG are specific for sympathetic neurons, ¹¹C-HED may be more specific for intravesicular uptake than ¹²³I-MIBG in some situations, such as that seen in reserpine pretreatment.