18F标记多巴胺D2受体显像剂在老龄及正常SD大鼠脑分布研究

Distribution of Dopamine D2 Receptor PET Imaging Agent 18F-Fallypride in the Brain of Normal and Aged Rats

  • 摘要: 为探索多巴胺D2受体与衰老的关系,采用亲核反应制备多巴胺D2受体PET显像剂18F-Fallypride,研究显像剂在老龄及正常SD大鼠的脑分区分布。通过尾静脉注射老龄及正常SD大鼠(3.7 MBq),注射显像剂后15 min行microPET显像,勾画纹状体为感兴趣区域,计算其标准化摄取值;PMOD软件对显像图融合分区,定量分析各脑分区标准化摄取值;显像后心室灌注,取全脑,冰冻切片,层厚20 μm,苏木素-伊红(HE)染色观察大鼠脑组织结构变化情况。结果表明,18F-Fallypride标记率>95%,放化纯度>98%,PBS放置2 h,放化纯仍大于95%。注射后15 min老龄及正常SD大鼠纹状体摄取18F-Fallypride的值分别为(0.58±0.11)%ID/g、(0.39±0.14)%ID/g;PMOD分区正常鼠扣带皮层、岛叶、下丘脑、嗅球、中脑等摄取值(分别为(0.120±0.012)%ID/g、(0.182±0.002)%ID/g、(0.111±0.002)%ID/g、(0.127±0.007)%ID/g、(0.083±0.012)%ID/g)低于老龄SD大鼠((0.154±0.013)%ID/g、(0.344±0.014)%ID/g、(0.244±0.019)%ID/g、(0.263±0.020)%ID/g、(0.216±0.012)%ID/g)(P<0.05);HE染色显示老龄SD大鼠部分神经元嗜酸性变或核破碎,偶伴有海绵状变形、层状或局灶性神经元坏死,其余无明显形态学改变。PET显像证实了多巴胺D2受体表达和脑老化之间的相关性,可为进一步深入研究疾病和药效的方法学提供依据。

     

    Abstract: With the progress of population aging, the incidence of agerelated disease has greatly increased. The dopamine D2 receptor is closely related to the age-related diseases, such as PD and AD. The PET imaging of the dopamine D2 receptor can provide noninvasive, dynamic, early and quantitative information on the function of the brain. So we intend to prepare dopamine D2 receptor PET imaging agent 18F-Fallypride and to study the disturbution of the agent in the brain of normal and aged rats, further to explore the relationship between dopamine D2 receptor and senility. 18F-Fallypride was prepared by nucleophilic reaction. And the PET image was performed in aged and normal rats 15 minutes after injection of the agent.Striatums were delineated as the region of interesting (ROI), the standard uptake value (SUV) of which was calculated. PMOD was used for image fusion, partition and quantitative analysis of standard uptake values of each brain area. After imaging, cardiac ventricle was perfused. The brain was obtained and frozen. The contour structure was observed by HE staining.The results showed that the labeling yield was over 95% and the radiochemical purity was higher than 98%. The stability was still over 95% 2 hours after incubation with PBS. The striatum uptake of 18F-Fallypride radioactivity in aged and normal rats 15 minutes after injection were (0.58±0.11)%ID/g, (0.39±0.14)%ID/g. The uptake of cortex cingulate, cortex insular, hypothalamus, olfactory, midbrain in normal rats ((0.120±0.012)%ID/g, (0.182±0.002)%ID/g, (0.111±0.002)%ID/g, (0.127±0.007)%ID/g, (0.083±0.012)%ID/g respectively) were inferior to aged rats ((0.154±0.013)%ID/g, (0.344±0.014)%ID/g, (0.244±0.019)%ID/g, (0.263±0.020)%ID/g, (0.216±0.012)%ID/g), which was displayed by PMOD. HE staining showed severe brain injury in elderly SD rats. Some neurons in the aged SD rats appeared acidophil change or nuclear fragmentation, accompanied by spongy deformation, lamellar or focal neuronal necrosis, and no obvious morphological changes. The relevance between dopamine D2 receptor and senility was demonstrated by PET imaging, which provided a basis for further research on the methodology of disease and pharmacodynamics research.

     

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