In vivo imaging of the brain vesicular monoamine transporter.
In vivo imaging of the brain vesicular monoamine transporter.
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发表时间：
1995-12
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通讯作者：
T. Vander Borght;M. Kilbourn;R. Koeppe;J. DaSilva;J. Carey;D. Kuhl;K. Frey
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作者：
T. Vander Borght;M. Kilbourn;R. Koeppe;J. DaSilva;J. Carey;D. Kuhl;K. Frey
在寻找单胺神经末梢完整性的体内标记物时，我们研究了甲氧基丁苯那嗪（MTBZ）作为脑突触囊泡单胺转运蛋白（VMAT 2）的示踪剂。方法首先研究了MTBZ在啮齿动物体内的生物分布、代谢和结合特异性，并估算了人体剂量。随后，在给予[11 C]MTBZ后，在正常志愿者中测定VMAT 2结合的人脑分布。获得脑区域时间-活动曲线，并使用动脉血采样和二室示踪动力学模型计算参数运输和结合图像。结果注射[3 H]MTBZ后15 min，大鼠脑内单胺神经末梢密度与已知的一致，以纹状体、外侧隔、黑质、中缝核和蓝斑的单胺神经末梢密度最高。此时，色谱法显示超过82%的脑活性，但不到47%的血浆活性对应于真实的MTBZ。在体内[11 C]MTBZ结合在小鼠脑中被抑制过量的未标记的二氢丁苯那嗪共注射。在人类中，[11 C]MTBZ具有高的初始脑摄取和从所有区域的快速清除，在高VMAT 2浓度区域的保留时间最长。VMAT 2密度的参数定量显示壳核和尾状核中的分布体积最高，大脑皮层和小脑中的分布体积较低。结论11碳MTBZ是PET定量测定人脑囊泡单胺转运体的合适配体。
UNLABELLED In the search for an in vivo marker of monoamine nerve terminal integrity, we investigated methoxytetrabenazine (MTBZ) as a tracer of the brain synaptic vesicular monoamine transporter (VMAT2). METHODS The biodistribution, metabolism and in vivo specificity of MTBZ binding were first evaluated in rodents and the human dosimetry was estimated. Subsequently, the human brain distribution of VMAT2 binding was determined in normal volunteers following administration of [11C]MTBZ. Brain regional time-activity curves were obtained, and parametric transport and binding images were calculated using arterial blood sampling and a two-compartment tracer kinetic model. RESULTS Regional rat brain localization of [3H]MTBZ 15 min postinjection was consistent with the known monoamine nerve terminal density, which demonstrated the highest activity in the striatum, lateral septum, substantia nigra pars compacta, the raphe nuclei and the locus coeruleus. At this time, chromatography revealed over 82% of brain activity, but less than 47% of plasma activity corresponded to authentic MTBZ. In vivo [11C]MTBZ binding in the mouse brain was inhibited by coinjection of excess unlabeled dihydrotetrabenazine. In humans [11C]MTBZ had high initial brain uptake and rapid clearance from all regions, with longest retention in areas of high VMAT2 concentration. Parametric quantification of VMAT2 density revealed the highest distribution volume in the putamen and caudate with lower values in cerebral cortex and cerebellum. CONCLUSION Carbon-11-MTBZ is a suitable ligand for PET quantification of the vesicular monoamine transporter in the human brain.