Quantitative analysis of dopamine transporters in human brain using [11C]PE2I and positron emission tomography: evaluation of reference tissue models
Quantitative analysis of dopamine transporters in human brain using [11C]PE2I and positron emission tomography: evaluation of reference tissue models
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DOI：
10.1007/s12149-010-0364-z
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发表时间：
2010-05-01
影响因子：
2.6
通讯作者：
Suhara, Tetsuya
中科院分区：
文献类型：
--
作者：
Seki, Chie;Ito, Hiroshi;Suhara, Tetsuya
多巴胺转运蛋白（Dopamine transporter， DAT）是突触前多巴胺再摄取载体，调节多巴胺能神经传递。[C-11]PE2I是一种可卡因类似物，作为一种有效的正电子发射断层扫描（PET）配体，具有高选择性的DAT。本研究的目的是评估参考组织模型定量方法对[C-11]PE2I的适用性。对6名年轻健康男性志愿者静脉注射[C-11]PE2I后进行动态PET扫描。获得经代谢物校正的动脉血浆输入功能。通过室模型分析和等离子体输入Logan分析确定动力学参数和分布体积（V (T)）。以脑区V (T)与小脑区V (T)之比计算分布容积比（DVR）。采用原始的多线性参考组织模型法（MRTMo）和简化的参考组织模型法（SRTM）确定dvr，并将结果与使用动脉输入函数的图形分析结果进行比较。为了估计使用参考组织模型计算的DVR误差，进行了小脑动力学和扫描时间的模拟研究。[C-11]PE2I结合最高的部位是纹状体，其次是中脑和丘脑。在描述小脑[C-11]PE2I动力学时，2组织模型优于1组织模型。测量数据和90分钟模拟数据都表明，参考组织模型导致纹状体DVR的低估。模拟结果表明，当小脑动力学描述为1组织模型时，90分钟的扫描时间是不够的。然而，MRTMo和SRTM测定的DVR值与其他下结合区图形法测定的DVR值一致。由于[C-11]PE2I在小脑中的动力学和C-11的有限扫描时间，MRTMo和SRTM低估了纹状体DVR。尽管存在这种局限性，本研究证明了参考组织模型的适用性。由于中脑和丘脑的DAT在神经精神疾病的病理生理学中很重要，这种非侵入性的定量分析将对临床研究有用。
Dopamine transporter (DAT) is a reuptake carrier of dopamine at presynapse that regulates dopaminergic neural transmission. [C-11]PE2I is a cocaine analog developed as a potent positron emission tomography (PET) ligand for DAT with high selectivity. The aim of this study was to evaluate the applicability of quantification methods using reference tissue models for [C-11]PE2I.Dynamic PET scans were performed in 6 young healthy male volunteers after an intravenous bolus injection of [C-11]PE2I. Metabolite-corrected arterial plasma-input functions were obtained. Compartment model analysis and plasma-input Logan analysis were performed to determine the kinetic parameters and distribution volume (V (T)). The distribution volume ratio (DVR) was calculated as the ratio of V (T) in the cerebral region to that in the cerebellum. DVRs were also determined by the original multilinear reference tissue model method (MRTMo) and the simplified reference tissue model method (SRTM), comparing the results with those obtained from graphical analysis using arterial input function. To estimate errors in DVR calculated using the reference tissue model, a simulation study that focused on cerebellar kinetics and scan duration was performed.The highest [C-11]PE2I binding was observed in the striatum, followed by the midbrain and thalamus. The 2-tissue model was preferable to the 1-tissue model for describing the [C-11]PE2I kinetics in the cerebellum. Both the measured and 90-min simulated data showed that reference tissue models caused an underestimation of DVR in the striatum. The simulation showed that 90-min scan duration was insufficient when cerebellar kinetics was described as a 1-tissue model. Nevertheless, DVR values determined by MRTMo and SRTM were in good agreement with those by the graphical approach in other lower binding regions.Due to the [C-11]PE2I kinetics in the cerebellum and limited scan duration for C-11, MRTMo and SRTM underestimated the striatal DVR. Despite this limitation, the present study demonstrated the applicability of reference tissue models. Since DAT in the midbrain and thalamus is of interest in the pathophysiology of neuropsychiatric disease, this noninvasive quantitative analysis will be useful for clinical investigations.