Schlösser R, Brodie J D, Dewey S L, Alexoff D, Wang G J, Fowler J S, Volkow N, Logan J, Wolf A P
Department of Psychiatry NYU Medical Center, New York, New York 10016, USA.
Synapse. 1998 Jan;28(1):66-70. doi: 10.1002/(SICI)1098-2396(199801)28:1<66::AID-SYN8>3.0.CO;2-A.
There is evidence for the shift of regulatory setpoints of functionally linked neurotransmitter systems as a basis of psychiatric disorders. 11C-raclopride PET, which has been shown to be sensitive to changes in endogenous dopamine and has a high short-term test-retest reliability, can be used to investigate different regulatory states of the dopaminergic system with respect to psychiatric diseases and pharmacological influences. Prior to these studies, the reliability of the method over time has to be established. The current study was performed in order to evaluate the long-term stability of the striatal dopaminergic system. Eight normal healthy subjects (mean age: 48.1 years; range: 24-75) were studied twice with 11C-raclopride PET two times under resting conditions with a mean time interval between the scans of 11.3 months (range: 1-19). The ratio of basal ganglia (BG) to cerebellar (CB) distribution volumes (DVs) revealed a mean absolute change of 6.94 (range: 0.0-12.87%) between study A and B. BG DVs mean absolute change was 6.30% (range: 0.55-30.46%), CB DVs mean absolute change was 8.65% (range: 3.51-16.33%). The mean change of the BG/CB ratio was -0.33% (range: 12.87-12.34%). BG DVs mean change was 4.55% (range: 4.2-30.46%), CB DVs mean change was 5.10% (range: -10.71-16.33%). The intraindividual differences between the two scans in our study were not significantly different as compared to the 24 hour interval test-retest data, which have been published earlier (repeated measures ANOVA with df = 11; F = 0.49; P = 0.50) [Volkow et al. (1993) J. Nucl. Med., 34:609-613]. The intraclass correlation of the DV ratio index was r = 0.81. The binding potential in the baseline scans and repeated scans showed a non-significant correlation with age (r = -0.58, P = 0.13). Interindividually, the DV ratio index revealed a mean of 3.18 (range = 2.55-3.68, SD = 0.42 in study A and of 3.16 (range 2.37-3.57, SD = 0.41) in study B. The intrasubject stability of the 11C-raclopride binding over a long-term period in normal human subjects suggests the feasibility of study designs investigating the long-term changes of the dopaminergic responsivity after pharmacological challenges. The baseline stability will also serve as a necessary reference for further dose-response studies and investigations of subchronical pharmacological interventions.
有证据表明，功能相关神经递质系统的调节设定点发生改变是精神疾病的基础。11C-雷氯必利PET已被证明对内源性多巴胺的变化敏感，且具有较高的短期重测可靠性，可用于研究多巴胺能系统在精神疾病和药物影响方面的不同调节状态。在进行这些研究之前，必须确定该方法随时间的可靠性。本研究旨在评估纹状体多巴胺能系统的长期稳定性。八名正常健康受试者（平均年龄：48.1岁；范围：24 - 75岁）在静息状态下接受了两次11C-雷氯必利PET检查，两次扫描之间的平均时间间隔为11.3个月（范围：1 - 19个月）。基底神经节（BG）与小脑（CB）分布容积（DVs）的比值显示，研究A和研究B之间的平均绝对变化为6.94（范围：0.0 - 12.87%）。BG DVs的平均绝对变化为6.30%（范围：0.55 - 30.46%），CB DVs的平均绝对变化为8.65%（范围：3.51 - 16.33%）。BG/CB比值的平均变化为 -0.33%（范围：12.87 - 12.34%）。BG DVs的平均变化为4.55%（范围：4.2 - 30.46%），CB DVs的平均变化为5.10%（范围： -10.71 - 16.33%）。与之前发表的24小时间隔重测数据相比，本研究中两次扫描的个体内差异无显著差异（重复测量方差分析，自由度 = 11；F = 0.49；P = 0.50）[沃尔科夫等人（1993年）《核医学杂志》，34：609 - 613]。DV比值指数的组内相关性为r = 0.81。基线扫描和重复扫描中的结合潜能与年龄无显著相关性（r = -0.58，P = 0.13）。个体间，DV比值指数在研究A中的平均值为3.18（范围 = 2.55 - 3.68，标准差 = 0.42），在研究B中的平均值为3.16（范围2.37 - 3.57，标准差 = 0.41）。正常人类受试者中11C-雷氯必利结合的长期受试者内稳定性表明，研究药物激发后多巴胺能反应性长期变化的研究设计是可行的。基线稳定性也将作为进一步剂量反应研究和亚慢性药物干预研究的必要参考。
