Multitracer PET characterization of the biology of the cardiac sympathetic nervous system in healthy volunteers

Objectives Several studies with the SPECT compound ¹²³I-MIBG suggested regional heterogeneity of sympathetic innervation in the healthy myocardium, with frequently decreased uptake in the inferior wall. We sought to investigate this further by looking into neuronal biology using 3 PET tracers with different kinetic properties in healthy volunteers.

Methods A 2-day PET protocol was employed in 9 subjects without any evidence of disease (8 males; 32±13yrs; BMI=26±4). On day 1, perfusion was measured with N13-ammonia, followed by dynamic imaging with C11-epinephrine(EPI; marker of vesicular storage). On day 2, C11-hydroxyephedrine(HED; marker of neuronal uptake) and C11-phenylephrine(PHEN; marker of vesicular leakage & MAO activity) were employed. Using polarmap analysis, metabolite-corrected tracer retention and washout rates were compared globally and regionally in 5 myocardial walls.

Results Perfusion was homogeneous in all subjects. Globally, there was a significant difference in the retention of tracers (26±5%/min for EPI, 18±5 for HED, 9±2 for PHEN; P<0.0001). Washout was only observed for PHEN (1.1±0.1%/min), but not for EPI (0.0±0.3) and HED (-0.3±0.4). Regionally, no significant heterogeneity or difference of retention or washout was observed for any tracer.

Conclusions Our results suggest that the biology of sympathetic nerve terminals, including catecholamine uptake (as measured by HED retention), storage (as measured by EPI retention) and turnover (as measured by PHEN washout) is homogeneous in healthy subjects.This observation will serve as a foundation for detailed characterization of dysfunctional innervation in heart disease.