Sympathetic nervous system (SNS) dysfunction has been implicated in the pathogenesis of many clinical conditions including heart failure, myocardial infarction and sudden death. Non-invasive techniques using radiotracers for positron emission tomography have been employed to characterize the cardiac SNS. To date, [11C]meta-hydroxyephedrine (HED) is the most commonly used PET tracer in humans, but widespread clinical utility is limited because of the short half-life of 11C. The aim of this study is to examine the tracer kinetics of novel 18F-labeled PET tracer, N-[3-bromo-4-(3-[18F]fluoro-propoxy)-benzyl]-guanidine (LMI-1195) to assess myocardial presynaptic sympathetic nerve function in humans. Nine participants (healthy n=2; ischemic cardiomyopathy n=6, left ventricular (LV) ejection fraction (EF)=34±4); and non-ischemic cardiomyopathy n=1, EF=37%) underwent two separate PET imaging visits within one week. On visit [a] participants underwent 13NH3 and dynamic HED PET imaging. On visit [b], participants underwent dynamic LMI-1195 PET imaging. The order of testing was random. HED and LMI-1195 retention index (RI) and volume of distribution (DV) were quantified to assess presynaptic sympathetic nerve integrity. Global LV RI (7.20±1.60 vs. 7.30±2.30%/min) and defect size (% of LV; 19.6±9.5 vs. 18.5±8.2) were not different between LMI-1195 and HED respectively. In contrast, global DV (23.12±8.36 vs. 14.72±7.63) was significantly greater for LMI-1195 compared to HED (p<0.05). LMI-1195 RI (R2=0.77) and DV (R2=0.68) were highly correlated with HED (Figure 1). Preliminary data suggests that LMI-1195 yields a reliable estimate of cardiac sympathetic innervation as compared to HED. Due to the rapid blood clearance of LMI-1195, DV values were higher compared to HED.