Abstract
18F-FP-(+)-DTBZ is a novel PET radiotracer targeting vesicular monoamine transporter type 2 (VMAT2). The goal was to explore the image features in normal human brains with 18F-FP-(+)-DTBZ as a reference of molecular landmark for clinical diagnosis in Parkinson's disease (PD) and related disorders.Materials and MethodsA total of 22 healthy subjects (59.3±6.0 years old) including 7 men and 15 women were recruited for MRI and 18F-FP-(+)-DTBZ PET scans. A total number of 55 brain VOIs were selected for quantitation analysis. The regional specific uptake ratio (SUR) was calculated with occipital as reference from MRI-based spatially normalized 18F-FP-(+)-DTBZ images. Regional percentage SUR to that of anterior putamen was calculated. Average SUR images were displayed in 2D and 3D space to illustrate the image patterns. The correlation between age and regional VMAT2 uptake was also examined.ResultsVisual assessment showed symmetric uptake of 18F-FP-(+)-DTBZ and obviously highest in striatum, followed by nucleus accumbens, hypothalamus, substantia nigra, and raphe nuclei. Quantification analysis revealed striatal VMAT2 density of anterior putamen>posterior putamen>caudate nucleus. Other subcortical regions were with moderate VMAT2 distribution (6∼51% SUR of anterior putamen), while slightly lower VMAT2 was observed in cerebellum (10.60% SUR) and much lower in neocortex (<5% SUR). No significant correlation of SUR to age was found in subcortical regions.ConclusionUsing 18F-FP-(+)-DTBZ PET, we showed the 2D and 3D imaging features of the VMAT2 distribution in vivo in healthy aging brains. The in vivo imaging characteristics of VMAT2 is consistent with the expression of VMAT2 in a recent autopsy study. Therefore, 3D visualization and higher image quality of 18F-FP-(+)-DTBZ PET imaging might potentially be a powerful biomarker in detecting VMAT2 distribution of subcortical regions, and for Parkinson's disease and related neuropsychiatric disorders involving related monoaminergic systems.
Highlights
The type 2 vesicular monoamine transporter (VMAT2) is a protein responsible for pumping monoamine neurotransmitters, including dopamine (DA), norepinephrine (NE) and serotonin (SE), from the neuronal cytosol into synaptic vesicles
Other subcortical regions were with moderate vesicular monoamine transporter type 2 (VMAT2) distribution (6,51% specific uptake ratio (SUR) of anterior putamen), while slightly lower VMAT2 was observed in cerebellum (10.60% SUR) and much lower in neocortex (,5% SUR)
3D visualization and higher image quality of 18F-FP-(+)-DTBZ positron emission tomography (PET) imaging might potentially be a powerful biomarker in detecting VMAT2 distribution of subcortical regions, and for Parkinson’s disease and related neuropsychiatric disorders involving related monoaminergic systems
Summary
The type 2 vesicular monoamine transporter (VMAT2) is a protein responsible for pumping monoamine neurotransmitters, including dopamine (DA), norepinephrine (NE) and serotonin (SE), from the neuronal cytosol into synaptic vesicles. Measurement of the VMAT2 density in brain can serve as a diagnosis tool for many neuropsychiatric diseases related to monoaminergic dysfunction. Since more than 90% of VMAT2 locate in the dopamine nerve terminals [1], the in vivo estimation of VMAT2 density may have great help for the diagnosis and management of disorders associated with nigrostriatal degeneration, such as Parkinson’s disease (PD). Positron emission tomography (PET) imaging with the VMAT2 tracer 11Cdihydrotetrabenazine (11C-DTBZ) has been proven to be an objective marker of nigrostriatal terminal integrity [2]. DTBZ PET imaging has a high sensitivity for detecting dopaminergic integrity in both healthy subjects and PD patients [4,5,6]. The detailed imaging characteristics of VMAT2 distribution in healthy aging human brains with 18F-FP-(+)-DTBZ
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