Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, M5T 1R8, Toronto, Ontario, Canada.
Neuroimage. 2014 Jan 1;84:868-75. doi: 10.1016/j.neuroimage.2013.09.021. Epub 2013 Sep 21.
One of the cellular markers of neuroinflammation is increased microglia activation, characterized by overexpression of mitochondrial 18kDa Translocator Protein (TSPO). TSPO expression can be quantified in-vivo using the positron emission tomography (PET) radioligand [(18)F]-FEPPA. This study examined microglial activation as measured with [(18)F]-FEPPA PET across the adult lifespan in a group of healthy volunteers. We performed genotyping for the rs6971 TS.PO gene polymorphism to control for the known variability in binding affinity. Thirty-three healthy volunteers (age range: 19-82years; 22 high affinity binders (HAB), 11 mixed affinity binders (MAB)) underwent [(18)F]-FEPPA PET scans, acquired on the High Resolution Research Tomograph (HRRT) and analyzed using a 2-tissue compartment model. Regression analyses were performed to examine the effect of age adjusting for genetic status on [(18)F]-FEPPA total distribution volumes (VT) in the hippocampus, temporal, and prefrontal cortex. We found no significant effect of age on [(18)F]-FEPPA VT (F (1,30)=0.918; p=0.346), and a significant effect of genetic polymorphism (F (1,30)=8.767; p=0.006). This is the first in-vivo study to evaluate age-related changes in TSPO binding, using the new generation TSPO radioligands. Increased neuroinflammation, as measured with [(18)F]-FEPPA PET was not associated with normal aging, suggesting that healthy elderly individuals may serve as useful benchmark against patients with neurodegenerative disorders where neuroinflammation may be present.
神经炎症的一个细胞标志物是小胶质细胞的过度激活，其特征是线粒体 18kDa 移位蛋白（TSPO）的过度表达。TSPO 的表达可以使用正电子发射断层扫描（PET）放射性配体[18F]-FEPPA 在体内进行定量。本研究使用 [18F]-FEPPA PET 检查了一组健康志愿者在成年期的小胶质细胞激活情况。我们对 rs6971 TSPO 基因多态性进行了基因分型，以控制已知的结合亲和力变异性。33 名健康志愿者（年龄范围：19-82 岁；22 名高亲和力结合者（HAB），11 名混合亲和力结合者（MAB））接受了[18F]-FEPPA PET 扫描，使用高分辨率研究断层扫描（HRRT）获取并使用 2 组织隔室模型进行分析。回归分析用于检查年龄对海马体、颞叶和前额叶 [18F]-FEPPA 总分布容积（VT）的影响，同时调整遗传状态。我们发现年龄对 [18F]-FEPPA VT 没有显著影响（F（1，30）=0.918；p=0.346），而遗传多态性有显著影响（F（1，30）=8.767；p=0.006）。这是第一项使用新一代 TSPO 放射性配体评估 TSPO 结合与年龄相关变化的体内研究。使用 [18F]-FEPPA PET 测量的神经炎症增加与正常衰老无关，这表明健康的老年个体可能是神经退行性疾病患者的有用基准，因为这些患者可能存在神经炎症。
