Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
J Nucl Med. 2020 Aug;61(8):1200-1204. doi: 10.2967/jnumed.119.237735. Epub 2020 Jan 31.
The effects of tobacco smoking on the immune system of the brain are not well elucidated. Although nicotine is immunosuppressive, other constituents in tobacco smoke have inflammatory effects. PET imaging of the 18-kDa translocator protein (TSPO) provides a biomarker for microglia, the primary immunocompetent cells of the brain. This work compared brain TSPO levels in 20 tobacco smokers (abstinent for at least 2 h) and 20 nonsmokers using a fully quantitative modeling approach for the first time, to our knowledge. C-PBR28 (-((2-(methoxy-C)-phenyl)methyl)--(6-phenoxy-3-pyridinyl)acetamide) PET scans were acquired with arterial blood sampling to estimate the metabolite-corrected input function. C-PBR28 volumes of distribution were estimated throughout the brain with multilinear analysis. Statistical analyses revealed no evidence of significant differences in regional C-PBR28 volumes of distribution between smokers and nonsmokers (whole-brain Cohen = 0.09) despite adequate power to detect medium effect sizes. These findings inform previous PET studies reporting lower TSPO radiotracer concentrations in the brain (measured as SUV) for tobacco smokers than for nonsmokers by demonstrating the importance of accounting for radiotracer concentrations in plasma. These findings suggest that nonsmokers and smokers have comparable TSPO levels in the brain. Additional work with other biomarkers is needed to fully characterize the effects of tobacco smoking on the brain immune system.
吸烟对大脑免疫系统的影响尚未得到充分阐明。虽然尼古丁具有免疫抑制作用，但烟草烟雾中的其他成分具有炎症作用。18 kDa 转位蛋白（TSPO）的 PET 成像为小胶质细胞（大脑的主要免疫活性细胞）提供了生物标志物。据我们所知，这项工作首次使用完全定量建模方法比较了 20 名吸烟（至少戒断 2 小时）者和 20 名不吸烟者的大脑 TSPO 水平。使用动脉采血来估计代谢物校正的输入函数，获取 C-PBR28（-（2-（甲氧基-C）-苯基）甲基-（6-苯氧基-3-吡啶基）乙酰胺）PET 扫描。通过多线性分析估计整个大脑的 C-PBR28 分布容积。尽管有足够的能力检测到中等效应大小，但统计分析并未显示吸烟者和不吸烟者之间大脑 C-PBR28 分布容积存在显著差异（全脑 Cohen'=0.09）。这些发现通过证明在血浆中考虑放射性示踪剂浓度的重要性，为先前报告的吸烟者大脑 TSPO 放射性示踪剂浓度（以 SUV 测量）低于不吸烟者的 PET 研究提供了信息。这些发现表明，不吸烟者和吸烟者的大脑 TSPO 水平相当。需要使用其他生物标志物开展更多工作，以充分描述吸烟对大脑免疫系统的影响。
