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In Vivo Assessment of Vesicular Monoamine Transporter Type 2 in Dementia With Lewy Bodies and Alzheimer Disease

Victor L. Villemagne, MD; Nobuyuki Okamura, MD; Svetlana Pejoska, RN; John Drago, MD; Rachel S. Mulligan, PhD; Gaël Chételat, PhD; Uwe Ackermann, PhD; Graeme O’Keefe, PhD; Gareth Jones, BSc; Sylvia Gong, PhD; Henry Tochon-Danguy, PhD; Hank F. Kung, PhD; Colin L. Masters, MD; Daniel M. Skovronsky, MD; Christopher C. Rowe, MD
Arch Neurol. 2011;68(7):905-912. doi:10.1001/archneurol.2011.142.
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Objective To assess the diagnostic potential of imaging striatal monoaminergic terminal integrity with the vesicular monoamine transporter type 2 (VMAT2) radioligand 18F 9-fluropropyl-(+)-dihydrotetrabenazine ([18F]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 [18F]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 [18F]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, [18F]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 [18F]AV-133 allows assessment of nigrostriatal degeneration in Lewy body diseases. [18F]AV-133 can robustly detect reductions of dopaminergic nigrostriatal afferents in patients with DLB and assist in the differential diagnosis from AD.

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Figures

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Figure 1. A, Representative 9-fluropropyl-(+)-dihydrotetrabenazine ([18F]AV-133) tissue ratio (RT) positron emission tomography images in a healthy control (HC) (66-year-old man; Mini-Mental State Examination [MMSE] score, 30), a patient with dementia with Lewy bodies (DLB) (63 years old; MMSE score, 27; Hoehn-Yahr score, 1.0), a patient with Parkinson disease (PD) (61-year-old man; MMSE score, 29; Hoehn-Yahr score, 2.5), and a patient with Alzheimer disease (AD) (63-year-old man; MMSE score, 26). B, Statistical parametric mapping analysis showing significantly lower striatal [18F]AV-133 RT values in a patient with DLB than in an HC and a patient with AD. Significantly lower [18F]AV-133 RT values were also observed in the anterior midbrain of a patient with DLB compared with an HC. Color bars represent t values. P < .05, corrected for multiple comparisons.

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Figure 2. Boxplots of caudate nuclei and anterior and posterior putamen 9-fluropropyl-(+)-dihydrotetrabenazine ([18F]AV-133) positron emission tomography tissue ratio (RT) values from volumes of interest analysis in healthy controls (HCs) and patients with dementia with Lewy bodies (DLB), Parkinson disease (PD), and Alzheimer disease (AD). +Significantly different from HC (corrected P < .05).

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