神经激肽1受体配体[¹¹C]R116301的定量分析。

Quantification of the neurokinin 1 receptor ligand [¹¹C]R116301.

作者信息

Wolfensberger Saskia P, Maruyama Kaoru, van Berckel Bart N, Lubberink Mark, Airaksinen Anu J, Boellaard Ronald, Luurtsema Gert, Reddingius Wieb, Janssens Frans E, Veltman Dick J, Windhorst Albert D, Leysen Josée E, Lammertsma Adriaan A

机构信息

Department of Nuclear Medicine, Psychiatry, VU University Medical Centre, Amsterdam, The Netherlands.

出版信息

Nucl Med Commun. 2011 Oct;32(10):896-902. doi: 10.1097/MNM.0b013e328347e96f.

DOI:10.1097/MNM.0b013e328347e96f

PMID:21876400

Abstract

PURPOSE

Neurokinin 1 (NK1) receptors have been implicated in depression, anxiety, and pain perception. Recently, it was shown that, in the human brain, a specific NK1 receptor-related signal was obtained with the novel radioligand, [¹¹C]R116301, using positron emission tomography. The purpose of this study was to evaluate various methods for quantifying specific [¹¹C]R116301 binding.

METHODS

Two dynamic 90-min [¹¹C]R116301 scans, separated by 5 h, were performed in 11 healthy volunteers. In three patients, the second scan was performed after an oral blocking dose of 125 mg of aprepitant, whereas in the other eight, no intervention was performed (test-retest). Whole striatum was used as the tissue of interest, as it has the highest density of NK1 receptors. Cerebellum was used as the reference tissue.

RESULTS

Reference tissue models were stable with the simplified reference tissue model (SRTM) performing best. Average (± standard deviation) SRTM-derived mean nondisplaceable binding potential (BP(ND)) of all (first) baseline scans was 0.64±0.31 (n=11), which reduced to -0.01±0.03 (n=3) after aprepitant administration. Test-retest results showed low variability (14.0±10.7%) and excellent reliability, as indicated by the intraclass correlation coefficient (0.93). The ratio of standardized uptake values of striatum and cerebellum minus 1, an approximation of BP(ND), showed very low variability (6.2±3.1%) with excellent reliability (intraclass correlation coefficient=0.98), and correlated well with SRTM-derived BP(ND) (R²=0.96).

CONCLUSION

SRTM is the model of choice for quantifying [¹¹C]R116301 binding. Semiquantitative tissue ratios hold promise for routine clinical applications.

摘要

目的

神经激肽1（NK1）受体与抑郁、焦虑及痛觉有关。最近研究表明，在人脑内，使用正电子发射断层扫描，新型放射性配体[¹¹C]R116301可获得特定的NK1受体相关信号。本研究目的是评估多种定量[¹¹C]R116301特异性结合的方法。

方法

对11名健康志愿者进行两次间隔5小时的90分钟动态[¹¹C]R116301扫描。3名患者在口服125毫克阿瑞匹坦阻断剂量后进行第二次扫描，另外8名患者未进行干预（重测）。由于全纹状体具有最高密度的NK1受体，因此将其用作感兴趣组织。小脑用作参考组织。

结果

参考组织模型稳定，简化参考组织模型（SRTM）表现最佳。所有（第一次）基线扫描经SRTM得出的平均（±标准差）非置换结合潜能（BP(ND)）为0.64±0.31（n = 11），阿瑞匹坦给药后降至-0.01±0.03（n = 3）。重测结果显示变异性低（14.0±10.7%）且可靠性极佳，组内相关系数表明为0.93。纹状体与小脑标准化摄取值之比减去1（BP(ND)的近似值）显示变异性极低（6.2±3.1%）且可靠性极佳（组内相关系数 = 0.98），并与SRTM得出的BP(ND)高度相关（R² = 0.96）。