Initial comparison of ntPET with microdialysis measurements of methamphetamine-induced dopamine release in rats: Support for estimation of dopamine curves from PET data

Initial comparison of ntPET with microdialysis measurements of methamphetamine-induced dopamine release in rats: Support for estimation of dopamine curves from PET data
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DOI:
10.1007/s11307-007-0124-1
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发表时间:
2008-03-01
影响因子:
3.1
通讯作者:
Schiffer, Wynne K.
Schiffer, Wynne K.
中科院分区:
医学3区
文献类型:
--
作者:
Morris, Evan D.;Normandin, Marc D.;Schiffer, Wynne K.

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最近引入的一种数学方法用于从动态正电子发射断层扫描(PET)数据中提取神经递质释放的时间特征,并进行了测试。开发该方法的目的是希望通过揭示 PET 数据中神经递质 (nt) 动态的时间信息,研究人员能够为药物滥用及其治疗等精神疾病的机制提供新的线索。在这项研究中,我们将基于模型的方法“ntPET”应用于大鼠的 C-11-雷氯必利 PET 扫描,其中通过微透析和 PET 同时测定一侧纹状体对甲基苯丙胺微量输注的多巴胺能反应。将 C-11-雷氯必利摄取到未经治疗的对侧纹状体中作为 ntPET 模型的输入。基于模型的 ntPET 分析和微透析测量的直接比较证实,ntPET 产生的多巴胺曲线在时间(起飞时间和峰值时间)上与微透析曲线非常相似。两种方法的起飞时间和高峰时间的差异相当。这两种方法都没有检测到对照动物对药物的虚假多巴胺反应。 ntPET 估计值和微透析测量值之间的高度对应性有力地支持了以下观点:动态 C-11-雷氯必利 PET 数据中存在有关多巴胺释放的时间信息,并且可以通过 ntPET 对其进行可靠估计。该方法完全可以转化为人体 PET 成像。
A recently introduced mathematical method for extracting temporal characteristics of neurotransmitter release from dynamic positron emission tomography (PET) data was tested. The method was developed with the hope that by uncovering temporal information about neurotransmitter (nt) dynamics in PET data, researchers could shed new light on mechanisms of psychiatric diseases such as drug abuse and its treatment. In this study, we apply our model-based method, "ntPET", to C-11-raclopride PET scans of rats in which the dopaminergic response to a microinfusion of methamphetamine in one striatum was assayed simultaneously by microdialysis and PET. Uptake of C-11-raclopride into the untreated contralateral striatum was used as an input to the ntPET model. Direct comparisons of the model-based ntPET analysis and the microdialysis measurements confirmed that ntPET produced dopamine curves that were very similar in timing (takeoff and peak times) to the microdialysis curves. Variances in takeoff and peak times were comparable for the two methods. Neither method detected a false dopamine response to drug in a control animal. The high degree of correspondence between ntPET estimates and microdialysis measurements lends strong support to the idea that temporal information regarding dopamine release exists in dynamic C-11-raclopride PET data and that it can be estimated reliably via ntPET. The method is entirely translatable to human PET imaging.