Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging
Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging
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DOI：
10.1002/ana.410400609
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发表时间：
1996-12-01
影响因子：
11.2
通讯作者：
Kuhl, DE
中科院分区：
文献类型：
--
作者：
Frey, KA;Koeppe, RA;Kuhl, DE
我们提出了一种利用正电子发射断层扫描（PET）和[C-11]二氢四苯那嗪（DTBZ）测定2型囊泡单胺转运体（VMAT2）脑区域密度的方法，并应用于人类。先前的动物研究表明纹状体VMAT2密度与黑质多巴胺神经元的完整性呈线性相关，不受药物或损伤代偿调节。在本研究中，采用动力学室室模型从静脉注射示踪剂后的脑和血浆DTBZ时间过程估计血脑[C-11]DTBZ转运（K-1）和VMAT2结合位点密度（组织到血浆DTBZ分布体积，DV）。在对照组中，我们发现壳核DTBZ DV随着年龄的增长而减少，相当于每年特异性VMAT2结合损失0.77%。帕金森病（PD）患者在壳核（-61%）和尾状核（-43%）中特异性DTBZ DV减少。老年对照和PD患者的最低特异性壳核DTBZ DV没有重叠。目前的结果表明[C-11]DTBZ PET适合于客观量化黑质纹状体完整性，包括评估PD的进展及其可能的治疗改变。
We present development and human application of a method for determining the regional cerebral density of the type 2 vesicular monoamine transporter (VMAT2) using positron emission tomography (PET) and [C-11] dihydrotetrabenazine (DTBZ). Previous animal studies indicate striatal VMAT2 density is linearly related to the integrity of substantia nigra dopamine neurons and is not subject to drug- or lesion-compensatory regulation. In the present studies, kinetic compartmental modeling was employed to estimate blood-brain [C-11]DTBZ transport (K-1) and VMAT2 binding site density (tissue-to-plasma DTBZ distribution volume, DV) from the cerebral and plasma DTBZ time courses after intravenous tracer injection. In controls, we found reductions of putamen DTBZ DV with advancing age, corresponding to losses of 0.77% per year in specific VMAT2 binding. Parkinson's disease (PD) patients had reduction in specific DTBZ DV in the putamen (-61%) and in the caudate nucleus (-43%). There was no overlap of lowest specific putamen DTBZ DV between individual elderly controls and PD patients. The present results indicate the suitability of [C-11]DTBZ PET for objective quantification of nigrostriatal integrity, including evaluation of PD progression and its possible therapeutic modification.