Quantification of Cardiac Sympathetic Nerve Density with N-11C-Guanyl-meta-Octopamine and Tracer Kinetic Analysis

Most cardiac sympathetic nerve radiotracers are substrates of the norepinephrine transporter (NET). Existing tracers such as 123I-metaiodobenzylguanidine (123I-MIBG) and 11C-(–)-meta-hydroxy-ephedrine (11C-HED) are flow-limited tracers because of their rapid NET transport rates. This prevents successful application of kinetic analysis techniques and causes semiquantitative measures of tracer retention to be insensitive to mild-to-moderate nerve losses. N-11C-guanyl-(–)-meta-octopamine (11C-GMO) has a much slower NET transport rate and is trapped in storage vesicles. The goal of this study was to determine whether analyses of 11C-GMO kinetics could provide robust and sensitive measures of regional cardiac sympathetic nerve densities.Methods: PET studies were performed in a rhesus macaque monkey under control conditions or after intra-venous infusion of the NET inhibitor desipramine (DMI). Five desipra-mine dose levels were used to establish a range of available cardia