]-guanidine (18 F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The 18 F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of 18 F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Methods: Healthy New Zealand White rabbits were studied with 18 F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of 18 F-LMI1195. Imaging was performed under norepineph-rine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of 11 C-hydroxyephedrine and 123 I-metaiodobenzylguanidine (123 I-MIBG) was examined by PET and planar scintigraphy, respectively. Results: Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for 11 C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and 18 F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased 11 C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P , 0.001), whereas 18 F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac 123 I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). Conclusion: In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of 18 F-LMI1195, 11 C-hydroxyephedrine, and 123 I-MIBG in rabbit hearts. 11 C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and release at the nerve terminals. In contrast, 18 F-LMI1195 and 123 I-MIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover.