Martin W R, Palmer M R, Patlak C S, Calne D B
Division of Neurology, University of British Columbia, Vancouver, Canada.
Ann Neurol. 1989 Oct;26(4):535-42. doi: 10.1002/ana.410260407.
The dopamine depletion that is characteristic of Parkinson's disease has been hypothesized to result from the combination of environmentally induced subclinical damage to the substantia nigra and the age-related loss of additional nigral neurons. Essential to this hypothesis is the existence of deteriorating function in the nigrostriatal pathway with advancing age. The present study was undertaken with [18F]6-fluoro-L-dopa and positron emission tomography to determine in vivo the effects of age on the nigrostriatal pathway in a series of 10 asymptomatic subjects (age range, 22-80 years; mean, 49.8 years). A graphical approach was used in the analysis of multiple-time tracer-uptake data to establish the presence of a compartment with unidirectional uptake and to calculate the rate constant, K, for uptake of [18F]6-fluoro-L-dopa from blood to striatum during steady-state, an index of the functional integrity of nigrostriatal nerve endings. There was a significant linear relationship between K and age (r = 0.80, p less than 0.005) with a decrease of 53.3% over the age range studied. These results demonstrate the application of a unidirectional transfer model to the analysis of [18F]6-fluoro-L-dopa and positron emission tomography data and provide in vivo confirmation of an age-related impairment of nigrostriatal function.
帕金森病的典型特征是多巴胺耗竭，据推测这是由环境因素导致的黑质亚临床损伤与年龄相关的额外黑质神经元丢失共同作用的结果。该假说的关键在于黑质纹状体通路功能会随着年龄增长而恶化。本研究采用[18F]6-氟-L-多巴和正电子发射断层扫描技术，对10名无症状受试者（年龄范围22 - 80岁；平均49.8岁）进行体内研究，以确定年龄对黑质纹状体通路的影响。在分析多次示踪剂摄取数据时采用了一种图形化方法，以确定存在单向摄取的隔室，并计算稳态期间[18F]6-氟-L-多巴从血液到纹状体摄取的速率常数K，它是黑质纹状体神经末梢功能完整性的一个指标。K与年龄之间存在显著的线性关系（r = 0.80，p < 0.005），在所研究的年龄范围内下降了53.3%。这些结果证明了单向转移模型在[18F]6-氟-L-多巴和正电子发射断层扫描数据分析中的应用，并在体内证实了黑质纹状体功能存在与年龄相关的损害。
