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

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Abstract

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.

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