Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan ; Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan ; Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
PLoS One. 2013 Sep 30;8(9):e75952. doi: 10.1371/journal.pone.0075952. eCollection 2013.
(18)F-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 (18)F-FP-(+)-DTBZ as a reference of molecular landmark for clinical diagnosis in Parkinson's disease (PD) and related disorders.
A total of 22 healthy subjects (59.3±6.0 years old) including 7 men and 15 women were recruited for MRI and (18)F-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 (18)F-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.
Visual assessment showed symmetric uptake of (18)F-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.
Using (18)F-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 (18)F-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.
(18)F-FP-(+)-DTBZ 是一种新型的正电子发射断层扫描(PET)放射性示踪剂,用于靶向囊泡单胺转运体 2(VMAT2)。本研究旨在通过使用(18)F-FP-(+)-DTBZ 作为分子标志物,探索其在正常人类大脑中的影像特征,以期为帕金森病(PD)和相关疾病的临床诊断提供参考。
共招募 22 名健康受试者(59.3±6.0 岁,包括 7 名男性和 15 名女性)进行 MRI 和(18)F-FP-(+)-DTBZ PET 扫描。共选择了 55 个大脑感兴趣区(VOI)进行定量分析。基于 MRI 空间归一化的(18)F-FP-(+)-DTBZ 图像,以枕叶为参考计算局部比摄取率(SUR)。计算局部与前壳核 SUR 的比值。以 2D 和 3D 空间显示平均 SUR 图像,以说明图像模式。还检查了年龄与局部 VMAT2 摄取之间的相关性。
视觉评估显示(18)F-FP-(+)-DTBZ 摄取对称,纹状体摄取最高,其次是伏隔核、下丘脑、黑质和中缝核。定量分析显示,壳核的 VMAT2 密度从前壳核>后壳核>尾状核。其他皮质下区域的 VMAT2 分布中等(前壳核的 6∼51% SUR),小脑(10.60% SUR)稍低,新皮质(<5% SUR)更低。皮质下区域的 SUR 与年龄无显著相关性。
使用(18)F-FP-(+)-DTBZ PET,我们展示了健康衰老大脑中 VMAT2 分布的 2D 和 3D 成像特征。体内 VMAT2 的成像特征与最近一项尸检研究中 VMAT2 的表达一致。因此,(18)F-FP-(+)-DTBZ PET 成像的 3D 可视化和更高的图像质量可能成为检测皮质下区域 VMAT2 分布的有力生物标志物,有助于帕金森病和涉及相关单胺能系统的相关神经精神疾病的诊断。