Characterization of extrastriatal D2 in vivo specific binding of [18F](N-methyl)benperidol using PET
Characterization of extrastriatal D2 in vivo specific binding of [18F](N-methyl)benperidol using PET
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DOI：
10.1002/syn.21566
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发表时间：
2012-09-01
期刊：
影响因子：
2.3
通讯作者：
Hershey, Tamara
中科院分区：
文献类型：
--
作者：
Eisenstein, Sarah A.;Koller, Jon M.;Hershey, Tamara
关于多巴胺 D2 受体家族在运动和神经精神疾病中的作用的 PET 成像研究受到使用放射性配体的限制，这些放射性配体对 D2 和 D3 受体亚型具有几乎相同的亲和力，并且容易与内源性多巴胺竞争。相比之下，放射性配体[18F]N-甲基苯哌啶醇([18F]NMB)对D2受体亚型(D2R)具有高选择性和亲和力，并且对内源性多巴胺不敏感。尽管 [18F]NMB 在纹状体中具有高结合水平，但其在纹状体外区域测量 D2R 的效用尚不清楚。构建了 14 名健康成年参与者的复合 MR-PET 图像，代表 [18F]NMB 注射后 60 至 120 分钟的平均 NMB 摄取量。使用寻峰算法确定区域峰值放射性。 FreeSurfer 和手动追踪确定了每个人的 MR 图像上的先验感兴趣区域 (ROI)，并从配准的 PET 图像中提取了组织活动曲线。 [18F]NMB结合电位(BPND)使用Logan图解法以小脑作为参考区域计算。在八名独特的参与者中，对 Logan 图法和三室动力学示踪模型之间的纹状体外 BPND 估计进行了比较。放射性和 BPND 水平在纹状体中最高，在纹状体外皮质下区域较低，在相对于小脑的皮质区域最低。年龄与纹状体 BPND 呈负相关。 BPND 对纹状体外 ROI 的估计在动力学和图形方法中高度相关。我们的研究结果表明，PET 与 [18F]NMB 测量纹状体外区域的特异性结合，使其成为研究健康和患病状态下纹状体外 D2R 水平的可行放射性配体。 Synapse 66:770780, 2012。(c) 2012 Wiley periodicals, Inc.
PET imaging studies of the role of the dopamine D2 receptor family in movement and neuropsychiatric disorders are limited by the use of radioligands that have near-equal affinities for D2 and D3 receptor subtypes and are susceptible to competition with endogenous dopamine. By contrast, the radioligand [18F]N-methylbenperidol ([18F]NMB) has high selectivity and affinity for the D2 receptor subtype (D2R) and is not sensitive to endogenous dopamine. Although [18F]NMB has high binding levels in striatum, its utility for measuring D2R in extrastriatal regions is unknown. A composite MR-PET image was constructed across 14 healthy adult participants representing average NMB uptake 60 to 120 min after [18F]NMB injection. Regional peak radioactivity was identified using a peak-finding algorithm. FreeSurfer and manual tracing identified a priori regions of interest (ROI) on each individual's MR image and tissue activity curves were extracted from coregistered PET images. [18F]NMB binding potentials (BPNDs) were calculated using the Logan graphical method with cerebellum as reference region. In eight unique participants, extrastriatal BPND estimates were compared between Logan graphical methods and a three-compartment kinetic tracer model. Radioactivity and BPND levels were highest in striatum, lower in extrastriatal subcortical regions, and lowest in cortical regions relative to cerebellum. Age negatively correlated with striatal BPNDs. BPND estimates for extrastriatal ROIs were highly correlated across kinetic and graphical methods. Our findings indicate that PET with [18F]NMB measures specific binding in extrastriatal regions, making it a viable radioligand to study extrastriatal D2R levels in healthy and diseased states. Synapse 66:770780, 2012. (c) 2012 Wiley Periodicals, Inc.