Hillmer AT, Matuskey D, Huang Y, et al. - Researchers sought to determine the effects of tobacco smoking on the immune system of the brain. PET imaging of the 18-kDa translocator protein (TSPO) yields a biomarker for microglia, the primary immunocompetent cells of the brain. In this study, brain TSPO levels in 20 tobacco smokers (abstinent for at least 2 h) were compared with those of 20 nonsmokers using a fully quantitative modeling approach for the first time. Researchers here acquired ¹¹C-PBR28 (N-((2-(methoxy-¹¹C)-phenyl)methyl)-N-(6-phenoxy-3-pyridinyl)acetamide) PET scans with arterial blood sampling to determine the metabolite-corrected input function. In statistical analyses, smokers and nonsmokers did not differ significantly in regional 11C-PBR28 volumes of distribution despite adequate power to detect medium effect sizes. Findings thereby inform prior PET studies inscribing lower TSPO radiotracer concentrations in the brain (measured as SUV) for tobacco smokers than for nonsmokers by establishing the relevance of addressing radiotracer concentrations in plasma. Among nonsmokers and smokers, comparable TSPO levels were identified in the brain.