Jucaite Aurelija, Odano Ikuo, Olsson Hans, Pauli Stefan, Halldin Christer, Farde Lars
Department of Woman and Child Health, Karolinska Institutet,, Stockholm, Sweden.
Eur J Nucl Med Mol Imaging. 2006 Jun;33(6):657-68. doi: 10.1007/s00259-005-0027-9. Epub 2006 Mar 3.
The dopamine transporter (DAT) is a plasma membrane protein of central interest in the pathophysiology of neuropsychiatric disorders and is known to be a target for psychostimulant drugs. [(11)C]PE2I is a new radioligand which binds selectively and with moderate affinity to central DAT, as has been demonstrated in vitro by autoradiography and in vivo by positron emission tomography (PET). The aims of the present PET study were to quantify regional [(11)C]PE2I binding to DAT in the human brain and to compare quantitative methods with regard to suitability for applied clinical studies.
One PET measurement was performed in each of eight healthy male subjects. The binding potential (BP) values were obtained by applying kinetic compartment analysis, which uses the metabolite-corrected arterial plasma curve as an input function. They were compared with the BP values quantified by two reference tissue approaches, using cerebellum as a reference region representing free and non-specific radioligand binding.
The radioactivity concentration was highest in the striatum, lower in the midbrain and very low in the cerebellum. The regional [(11)C]PE2I binding could be interpreted by kinetic compartment models. However, the BP values in the striatum obtained by the compartment analyses were about 30% higher than the BP values obtained using reference tissue methods. We suggest that the difference may be explained by the inaccurate metabolite correction, small amounts of radioactive metabolites that could account for the presence of non-specific binding in the cerebellum and insufficient data acquisition time.
The reference methods may be used to quantify [(11)C]PE2I binding in clinical studies, assuming that non-specific binding in the cerebellum does not vary between subjects and that an extended data acquisition time is employed. Moreover, the study corroborates the previous observation that [(11)C]PE2I is advantageous for PET examination of DAT binding in the midbrain, a region from which dopaminergic innervation originates and which is of central interest for the pathophysiology of several neuropsychiatric disorders.
多巴胺转运体（DAT）是神经精神疾病病理生理学中备受关注的一种质膜蛋白，并且已知它是精神兴奋药物的作用靶点。[（11）C]PE2I是一种新型放射性配体，已通过放射自显影体外实验以及正电子发射断层扫描（PET）体内实验证明，它能选择性且以中等亲和力与中枢DAT结合。本PET研究的目的是量化人脑区域内[（11）C]PE2I与DAT的结合，并比较不同定量方法在应用于临床研究方面的适用性。
对8名健康男性受试者每人进行一次PET测量。通过应用动力学房室分析获得结合势（BP）值，该分析使用经代谢物校正的动脉血浆曲线作为输入函数。将这些值与通过两种参考组织方法量化得到的BP值进行比较，使用小脑作为代表游离和非特异性放射性配体结合的参考区域。
纹状体中的放射性浓度最高，中脑较低，小脑极低。区域内[（11）C]PE2I结合可用动力学房室模型解释。然而，通过房室分析获得的纹状体BP值比使用参考组织方法获得的BP值高约30%。我们认为，这种差异可能是由于代谢物校正不准确、少量放射性代谢物可能导致小脑中存在非特异性结合以及数据采集时间不足所致。
假设小脑中的非特异性结合在受试者之间无差异且采用延长的数据采集时间，参考方法可用于临床研究中量化[（11）C]PE2I结合。此外，该研究证实了先前的观察结果，即[（11）C]PE2I有利于对中脑DAT结合进行PET检查，中脑是多巴胺能神经支配的起源区域，并且是几种神经精神疾病病理生理学的核心关注点。
