Hume S P, Lammertsma A A, Myers R, Rajeswaran S, Bloomfield P M, Ashworth S, Fricker R A, Torres E M, Watson I, Jones T
Cyclotron Unit, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
J Neurosci Methods. 1996 Aug;67(2):103-12.
The use of a recently commissioned small-diameter, high-resolution positron emission tomography (PET) to obtain a measure of specific binding of 3 carbon-11 labelled ligands in rat striatum is described. Using cerebellum as a reference tissue, compartmental modelling was used to obtain individual estimates of striatal binding potential (defined as the ratio of rate constants to and from the specifically bound compartment) for [11C]raclopride (D2 receptors), [11C]SCH 23390 (D1 receptors) and [11C]RTI-121 (dopamine transporter). The coefficients of variation in control, anaesthetized rats were of the order of 10%. Using two models of human disease, namely striatal injection of ibotenic acid to produce postsynaptic cell loss as in Huntington's disease, and 6-hydroxydopamine injection into substantia nigra pars compacta to mimic dopaminergic terminal loss in Parkinson's disease, marked reductions in binding potential were observed for the corresponding pre- or postsynaptic markers. When the regions of interest are so small as to be of the order of the spatial resolution of the system, factor such as spill over and partial volume negate absolute quantification of tissue radioactivity. Nevertheless, the use of PET to monitor relative changes in dopaminergic integrity should be considered as a viable complement to established in vivo microdialysis and post mortem techniques.
本文描述了使用最近启用的小直径、高分辨率正电子发射断层扫描（PET）来测量大鼠纹状体中3种碳-11标记配体的特异性结合。以小脑作为参考组织，采用房室模型分别估算[11C]雷氯必利（D2受体）、[11C]SCH 23390（D1受体）和[11C]RTI-121（多巴胺转运体）的纹状体结合潜力（定义为进出特异性结合房室的速率常数之比）。在麻醉的对照大鼠中，变异系数约为10%。利用两种人类疾病模型，即注射鹅膏蕈氨酸以造成纹状体突触后细胞缺失（如同亨廷顿病），以及向黑质致密部注射6-羟基多巴胺以模拟帕金森病中的多巴胺能终末缺失，观察到相应突触前或突触后标记物的结合潜力显著降低。当感兴趣区域小到与系统的空间分辨率处于同一量级时，诸如溢出和部分容积等因素会使组织放射性的绝对定量无效。尽管如此，PET用于监测多巴胺能完整性的相对变化仍应被视为现有体内微透析和死后技术的可行补充。
