Whole-Body Biodistribution and Radiation Dosimetry of <sup>18</sup>F-FP-(+)-DTBZ (<sup>18</sup>F-AV-133): A Novel Vesicular Monoamine Transporter 2 Imaging Agent

Lin, Kun-Ju; Weng, Yi-Hsin; Wey, Shiaw-Pyng; Hsiao, Ing‐Tsung; Lu, Chin‐Song; Skovronsky, Daniel; Chang, Hong‐Shiu; Kung, Mei‐Ping; Yen, Tzu‐Chen

doi:10.2967/jnumed.110.078196

Cited by 59 publications

(36 citation statements)

References 26 publications

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“…The present data confi rmed that AV-133 uptake assessed here is consistent with previous studies of the primate brain [21,25,32] . MPTP administration induced striatal dopaminergic denervation, and resulted in a decrease in VMAT2 expression (Fig.…”

Section: Discussionsupporting

confidence: 93%

Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging ([18F]AV-133)

et al. 2013

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The 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP)-induced parkinsonism model, particularly in non-human primates, remains the gold-standard for studying the pathogenesis and assessing novel therapies for Parkinson's disease. However, whether the loss of dopaminergic neurons in this model is progressive remains controversial, mostly due to the lack of objective in vivo assessment of changes in the integrity of these neurons. In the present study, parkinsonism was induced in cynomolgus monkeys by intravenous administration of MPTP (0.2 mg/kg) for 15 days; stable parkinsonism developed over 90 days, when the symptoms were stable. Noninvasive positron emission tomographic neuroimaging of vesicular monoamine transporter 2 with 9-[ 18 F] fluoropropyl-(+)-dihydrotetrabenazine ([ 18 F]AV-133) was used before, and 15 and 90 days after the beginning of acute MPTP treatment. The imaging showed evident progressive loss of striatal uptake of [ 18 F]AV-133. The dopaminergic denervation severity had a significant linear correlation with the clinical rating scores and the bradykinesia subscores. These

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Section: Discussionsupporting

confidence: 93%

Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging ([18F]AV-133)

et al. 2013

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“…18 F-DTBZ was prepared and synthesized at the cyclotron facility of Chang Gung Memorial Hospital as described previously (10,19). All subjects were studied in a Biograph mCT PET/CT System (Siemens Medical Solutions) with a 3-dimensional (3D) acquisition mode.…”

Section: Data Acquisitionmentioning

confidence: 99%

“…In the PD group, we defined the contralateral striatum as the striatum that was located opposite to the symptomatic limbs, and the contralateral striatum was evaluated separately from the ipsilateral striatum. According to our previous studies, the uptake of 18 F-DTBZ was symmetric in the healthy subjects (19,20). For further statistical analysis, the contralateral striatum was defined as the right striatum, and the ipsilateral striatum was defined as the left striatum in the control group.…”

Section: Image Analysismentioning

confidence: 99%

“…Animal studies conclude that 18 F-DTBZ is a sensitive and selective tracer for VMAT2 binding sites, and it may be useful for in vivo evaluation of diseases relating to changes of monoamine neuronal integrity (10,18). Our previous study showed that 18 F-DTBZ PET was safe, with appropriate biodistribution and radiation dosimetry for imaging VMAT2 sites in humans (19). Therefore, we conducted this study to evaluate the capability of 18 F-DTBZ PET imaging in detecting the monoaminergic degeneration in early PD in vivo and to test the sensitivity and specificity of 18 F-DTBZ PET in differentiating early PD from normal aging.…”

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confidence: 99%

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In Vivo Detection of Monoaminergic Degeneration in Early Parkinson Disease by ¹⁸F-9-Fluoropropyl-(+)-Dihydrotetrabenzazine PET

Lin

Hsiao

et al. 2013

J Nucl Med

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PET with 18 F-9-fluoropropyl-(1)-dihydrotetrabenzazine ( 18 F-DTBZ), a novel radiotracer targeting vesicular monoamine transporter type 2 (VMAT2), has been proven as a useful imaging marker to measure dopaminergic integrity. Methods: The aim of this study was to evaluate the capability of 18 F-DTBZ PET in detecting the monoaminergic degeneration in early Parkinson disease (PD) in vivo. Seventeen age-matched healthy subjects and 30 PD patients at early stage of disease (duration of disease # 5 y) with mild and unilateral motor symptoms underwent 18 F-DTBZ PET scans. The severity of disease, including Unified Parkinson Disease Rating Scale and modified Hoehn and Yahr Stage (mHY), were recorded at off-medication states. The standardized volumes of interest were applied to the spatial normalized image for quantification analysis. The specific uptake ratios (SURs) were calculated according to the formula (specific volumes-of-interest counts/occipital cortex counts) 2 1. SUR measurements were summarized for each brain region. Results: The mean duration of disease in the PD group was 3.2 6 2.1 y (range, 0.5-5 y). The mean mHY was 1.0 6 0.1 (range, 1-1.5). The SURs of bilateral caudate, anterior putamen, posterior putamen, substantia nigra, and nucleus accumbens were significantly lower in PD patients than those of healthy subjects. The reduction of SURs was most severe in the contralateral (the brain regions that are located opposite to the symptomatic side) posterior putamen (281%), followed by the ipsilateral posterior putamen (267%). Receiver-operating-characteristic curve analysis showed that the SURs of the bilateral posterior putamen and contralateral anterior putamen had a sensitivity of 100% and specificity of 100% in differentiating PD patients from healthy subjects. Conclusion: 18 F-DTBZ PET was as an excellent tool for the early diagnosis of PD. The obvious decline of 18 F-DTBZ uptake in the ipsilateral (asymptomatic) striatum suggested that 18 F-DTBZ PET might serve as an in vivo biomarker to detect the monoaminergic degeneration in the premotor phase of PD.

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“…The Mann-Whitney's U test was used in cerebral VMAT2, and has proved to be a potential quantitative biomarker for monitoring dopaminergic degeneration in Parkinson's disease (PD) [2][3][4]. One major limitation of the tracer preventing its wide use is its short physical halflife (20 min [5]. Previous studies show that 18 F-AV133 is a promising PET tracer for detecting and monitoring the VMAT2 reduction in PD patients [6][7][8][9][10][11].…”

Section: Plasma Lipid Indicator Evaluationmentioning

confidence: 99%

Associations between 18F-AV133 Cerebral VMAT2 Binding and Plasma LDL and HDL Levels in Parkinson’s Disease

Gao¹,

Zhang²,

Chen³

et al. 2016

J Neuroimaging Psychiatry Neurol

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Whole-Body Biodistribution and Radiation Dosimetry of ¹⁸F-FP-(+)-DTBZ (¹⁸F-AV-133): A Novel Vesicular Monoamine Transporter 2 Imaging Agent

Cited by 59 publications

References 26 publications

Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging ([18F]AV-133)

Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging ([18F]AV-133)

In Vivo Detection of Monoaminergic Degeneration in Early Parkinson Disease by ¹⁸F-9-Fluoropropyl-(+)-Dihydrotetrabenzazine PET

Associations between 18F-AV133 Cerebral VMAT2 Binding and Plasma LDL and HDL Levels in Parkinson’s Disease

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Whole-Body Biodistribution and Radiation Dosimetry of 18F-FP-(+)-DTBZ (18F-AV-133): A Novel Vesicular Monoamine Transporter 2 Imaging Agent

Cited by 59 publications

References 26 publications

Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging ([18F]AV-133)

Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging ([18F]AV-133)

In Vivo Detection of Monoaminergic Degeneration in Early Parkinson Disease by 18F-9-Fluoropropyl-(+)-Dihydrotetrabenzazine PET

Associations between 18F-AV133 Cerebral VMAT2 Binding and Plasma LDL and HDL Levels in Parkinson’s Disease

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Whole-Body Biodistribution and Radiation Dosimetry of ¹⁸F-FP-(+)-DTBZ (¹⁸F-AV-133): A Novel Vesicular Monoamine Transporter 2 Imaging Agent

In Vivo Detection of Monoaminergic Degeneration in Early Parkinson Disease by ¹⁸F-9-Fluoropropyl-(+)-Dihydrotetrabenzazine PET