A dopamine transporter (DAT) ligand 2β-carbomethoxy-3β-(4-fluoro-phenyl)-8-(2-[18F]fluoroethyl)nortropane ([18F]β-CFT-FE) was synthesized and evaluated in comparison with [11C]β-CFT in monkey brain using animal positron emission tomography (PET). [18F]β-CFT-FE and [11C]β-CFT were injected intravenously to conscious monkeys for a 91-min PET scan with arterial blood sampling for metabolite analysis. In the conscious state, [18F]β-CFT-FE provided a peak about 20 min after the injection and declined thereafter in the striatum of monkey brain, while [11C]β-CFT continuously increased with time up to 91 min after injection. Metabolite analysis revealed that [18F]β-CFT-FE was more rapidly metabolized in plasma than [11C]β-CFT. The striatal binding of both ligands was dose-dependently displaced by preadministration of a specific DAT inhibitor, GBR12909, at doses of 0.5 and 5 mg/kg; however, the displacement degree of [11C]β-CFT-FE was higher than that of [18F]β-CFT. The effects of the anesthetics, ketamine and isoflurane, on binding were more prominent in [11C]β-CFT than [18F]β-CFT-FE. Specificity and affinity of β-CFT-FE to DAT were evaluated in an in vitro assay using cloned human DAT, serotonin transporter, and norepinephrine transporter in comparison with other conventional DAT ligands, showing that β-CFT-FE had lower affinity and higher specificity to DAT than β-CFT and β-CIT. These results suggested that [18F]β-CFT-FE could be a potential imaging agent for DAT, providing excellent selectivity and tracer kinetics for quantitative PET imaging. Synapse 54:37–45, 2004. © 2004 Wiley-Liss, Inc.