OBJECTIVE: To assess the diagnostic potential of imaging striatal monoaminergic terminal integrity with the vesicular monoamine transporter type 2 (VMAT2) radioligand (18)F 9-fluropropyl-(+)-dihydrotetrabenazine ([(18)F]AV-133) and positron emission tomography to distinguish dementia with Lewy bodies (DLB) from Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS: Nine patients with DLB, 10 patients with AD, 20 patients with Parkinson disease (PD), and 10 healthy age-matched control subjects underwent [(18)F]AV-133 positron emission tomography studies. VMAT2 density was calculated through normalized tissue uptake value ratios at 120 to 140 minutes postinjection using the primary visual cortex as the reference region. MAIN OUTCOME MEASURE: Comparison of the tissue ratio for [(18)F]AV-133 between the different clinical diagnostic groups. RESULTS: Lower VMAT2 densities were observed in patients with DLB when compared with patients with AD especially in the posterior putamen (caudate: mean [SD], 1.24 [0.6] vs 2.83 [0.9]; P < .001; effect size = 2.1; anterior putamen: mean [SD], 0.90 [0.5] vs 3.01 [0.9]; P < .001; effect size = 2.9; posterior putamen: mean [SD], 0.62 [0.5] vs 2.87 [0.8]; P < .001; effect size = 3.4). Compared with healthy controls, [(18)F]AV-133 tissue ratios were significantly lower by 88% and 74% in the posterior putamen, 74% and 65% in the anterior putamen, and 53% and 51% in the caudate nucleus of patients with PD and DLB, respectively. In contrast to patients with PD and DLB, no reductions were observed in patients with AD. CONCLUSIONS: [(18)F]AV-133 allows assessment of nigrostriatal degeneration in Lewy body diseases. [(18)F]AV-133 can robustly detect reductions of dopaminergic nigrostriatal afferents in patients with DLB and assist in the differential diagnosis from AD.