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

Abstract

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.

Obfuscated volume rendering

“…As stated in [13], positron emission tomography (PET) scans of human brains could help in detecting Parkinson's Disease (PD) at an earlier stage. PET is a nuclear medicine, functional imaging technique, which detects the amount of radioactive substance (called radionuclide or radioactive tracer) that is injected into the subject in order to construct a three-dimensional image for further examination of the tissue under study.…”

“…PET is a nuclear medicine, functional imaging technique, which detects the amount of radioactive substance (called radionuclide or radioactive tracer) that is injected into the subject in order to construct a three-dimensional image for further examination of the tissue under study. It was addressed in [13] that by analyzing the reduction of the vesicular monoamine transporter 2 (VMAT2) density from the PET image, PD can be diagnosed effectively. VMAT2 is a specific presynaptic protein involved in the transport of monoamines from cytosol to storage vesicles of monoaminergic nerve terminals.…”

“…Are the results generated by the proposed obfuscated volume rendering approach as effective as the results yielded from a normal direct volume rendering technique? 13 Approximating the rendering of one single slice or any specifically chosen slices by rendering and compositing nearby sub-volumes.…”

Recent imaging advances in neurology

“…Recent studies have shown that novel neuroimaging tools could aid in the early diagnosis and monitoring of PD such as [ 18 F]DTBZ PET, a vesicular monoamine transporter 2 (VMAT-2) marker, for measuring dopaminergic terminal loss [5,6]. Semi-automated measurement of substantia nigra pars compacta (SNc) volume with 3D-neuromelanin sensitive MRI has been demonstrated to be able to distinguish PD patients from healthy subjects (HS), especially in the early stage of the disease [7].…”

A New Perspective on Parkinson’s Disease: Pathology Begins in the Gastrointestinal Tract

“…Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in the elderly population, following Alzheimer's disease (Lin et al, 2014). PD is a chronic disorder, characterized primarily by motor deficits including resting tremor, rigidity, bradykinesia, and postural instability (Burke & O'Malley, 2013;Choi et al, 2016;Lohr & Miller, 2014;Miller et al, 1999;Taylor et al, 2014).…”