Dopamine D2 Receptor Imaging with SPECT: Studies in Different Neuropsychiatric Disorders
Dopamine D2 Receptor Imaging with SPECT: Studies in Different Neuropsychiatric Disorders
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SPECT 多巴胺 D2 受体成像：不同神经精神疾病的研究
DOI：
10.1038/jcbfm.1991.53
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发表时间：
1991
影响因子：
6.3
通讯作者：
L. Deecke
中科院分区：
文献类型：
--
作者：
T. Brücke;I. Podreka;P. Angelberger;S. Wenger;A. Topitz;B. Küfferle;C. Müller;L. Deecke
本研究的目的是可视化和定量多巴胺D2受体在活体人脑中使用123 I标记的配体和单光子发射计算机断层扫描（SPECT）技术。S-（-）-碘苯甲酰胺[S-（-）-IBZM]在实验研究中已被证明是一种对D2受体具有高亲和力的高选择性配体。静脉注射5毫居里（185 MBq）的123 I标记的S-（-）-IBZM给12名对照受试者、22名接受L-多巴治疗的帕金森病患者、12名未接受L-多巴治疗的帕金森病患者、10名未接受药物治疗的亨廷顿病患者和12名接受不同抗精神病药物治疗的患者。注射后1小时开始用旋转双头闪烁照相机收集数据，持续50分钟。在半定量方法中，计算纹状体和侧额叶皮质区域中每个像素的平均计数之间的比率，对照组为1.74 ± 0.10。在患有亨廷顿氏病的患者中发现该比率显著降低（1.38 ± 0.12; p = 0.0001），在未经治疗的帕金森病患者中没有显著变化（1.67 ± 0.14），但在左旋多巴治疗的病例中降低（1.59 ± 0.13; p = 0.0014）。发现抗精神病药物的每日总剂量与该比率的降低之间存在曲线关系。在完全抗精神病药治疗下估计的受体阻滞为75- 80%。S-（-）-IBZM结合随年龄增加而降低（p < 0.01）。当使用IBZM的外消旋混合物时，特异性结合显著降低，并且没有观察到与R-（+）-异构体的特异性结合，证明IBZM结合的立体选择性。结果表明，以S-（-）-IBZM为配体，采用SPECT技术可以高分辨率清晰地显示多巴胺D2受体。半定量方法可以估计受体阻断或受体密度。该方法对退行性神经系统疾病如亨廷顿病的诊断和抗精神病药物治疗的监测具有临床价值。
The purpose of the present study is to visualize and quantify dopamine D2 receptors in the living human brain using an 123I-labeled ligand and the single photon emission computerized tomography (SPECT) technique. S-(–)-Iodobenzamide [S-(–)-IBZM] has been shown to be a highly selective ligand with high affinity for D2 receptors in experimental studies. Five millicuries (185 MBq) of 123I-labeled S-(–)-IBZM was administered intravenously to 12 control subjects, 22 parkinsonian patients under L-Dopa therapy, 12 parkinsonian patients without L-Dopa, 10 unmedicated patients with Huntington's disease, and 12 patients under different neuroleptics. Data collection with a rotating double-head scintillation camera started 1 h after injection and lasted for 50 min. In a semiquantitative approach, a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral frontal cortex, which was 1.74 ± 0.10 in the control group. A marked reduction of this ratio was found in patients with Huntington's disease (1.38 ± 0.12; p = 0.0001), no significant changes in untreated parkinsonian patients (1.67 ± 0.14), but a reduction in L-Dopa-treated cases (1.59 ± 0.13; p = 0.0014). A curvilinear relationship was found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under full neuroleptic treatment was 75–80%. S-(–)-IBZM binding was reduced with increasing age (p < 0.01). Specific binding was reduced markedly when the racemic mixture of IBZM was used, and no specific binding was seen with the R-(+)-isomer, demonstrating the stereoselectivity of IBZM binding. The results show that dopamine D2 receptors can be clearly visualized with high resolution using the SPECT technique and S-(–)-IBZM as a ligand. A semiquantitative approach can give estimates for receptor blockade or receptor density. This method is of clinical value for the diagnosis of degenerative neurological disorders such as Huntington's disease and for the monitoring of neuroleptic treatment.
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