Evaluation of Sympathetic Nerve Terminals With [ 11 C]Epinephrine and [ 11 C]Hydroxyephedrine and Positron Emission Tomography

Abstract

Background —The goal of the present study was to directly compare the new radiopharmaceutical agent [ 11 C]epinephrine (EPI) with [ 11 C]hydroxyephedrine (HED) through the use of PET. Methods and Results —Seven healthy volunteers and 10 patients were investigated after heart transplantation. PET images of both tracers were of excellent quality in the volunteers. Values for radiolabeled metabolites (measured in percent of blood activity) at 5, 20, and 60 minutes after injection were ≈35%, ≈82%, and ≈86% for EPI and ≈13%, ≈47%, and ≈78% for HED, respectively. At 35 minutes, metabolite-corrected mean myocardial retention fraction of EPI (0.235±0.022 min −1 ) was significantly greater ( P <0.01) than that of HED (0.142±0.012 min −1 ). Corrected tracer retention fractions of both EPI and HED were significantly reduced in transplant recipients (0.055±0.004 min −1 , P <0.0001; and 0.050±0.006 min −1 , P <0.0001, respectively) compared with volunteers. Normalization of retention fractions of patients with transplantation within 1 year to volunteers resulted in a value (ratio expressed in percent) of 20.6±1.8% for EPI, significantly ( P <0.03) smaller than 27.8±0.8% for HED. In patients with transplantation later than 1 year, the values were 26.0±2.9% for EPI compared with 44.2±5.6% for HED ( P <0.014). Conclusions —Both tracers showed high selectivity for neuronal uptake in the heart, with a significant reduction in tracer retention in transplant recipients compared with volunteers. Compared with HED, EPI showed greater retention in volunteers and a lower retention ratio in transplant recipients, suggesting that EPI may be the superior tracer with higher sensitivity to neuronal abnormalities. Because EPI reflects neuronal uptake, metabolism, and storage, it may be more suitable for the study of neuronal integrity than HED, which primarily traces uptake-1 capacity.