Tobacco Smoking in People Is Not Associated with Altered 18-kDa Translocator Protein Levels: A PET Study

Abstract

Rationale:The effects of tobacco smoking on the brain's immune system are not well elucidated. While nicotine is immunosuppressive, other constituents in tobacco smoke have inflammatory effects. Positron Emission Tomography (PET) imaging of the 18-kDa translocator protein (TSPO) provide a biomarker for microglia, the brain's primary immunocompetent cells. This work compared brain TSPO levels in 20 tobacco smokers (abstinent for at least 2 hours) and 20 nonsmokers using a fully quantitative modeling approach for the first time.Methods: [ 11 C]PBR28 PET scans were acquired with arterial blood sampling to estimate the metabolite-corrected input function. [ 11 C]PBR28 volumes of distribution (V T ) were estimated throughout the brain with multilinear analysis.Results: Statistical analyses revealed no evidence for significant differences in regional [ 11 C]PBR28 V T between smokers and non-smokers (whole-brain Cohen's d=0.09) despite adequate power to detect medium effect sizes.Conclusions: These findings inform previous PET studies reporting lower TSPO radiotracer concentrations in brain (measured as standardized uptake value, SUV) of tobacco smokers compared to nonsmokers by demonstrating the importance of accounting for radiotracer concentrations in plasma. These findings suggest that compared to nonsmokers, smokers have comparable TSPO levels in brain. Additional work with other biomarkers is needed to fully characterize effects of tobacco smoking on the brain's immune system.

Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers

“… Brody et al (2017) showed that smokers have lower TSPO receptor availability than healthy controls as measured with [ 11 C] DAA1106. A similar TSPO receptor availability study by Hillmer et al (2020) found no difference in TSPO levels between smokers and healthy controls. In Brody et al smokers were scanned in a satiated state and in Hillmer et al smokers were abstinent for 2–14 h. Future studies should assess TSPO receptor availability in smokers pre-treated with LPS compared to placebo and the effect of smoking abstinence.…”

Cigarette Smoke Exposure Induces Neurocognitive Impairments and Neuropathological Changes in the Hippocampus

“…Interestingly, a clinical study exploring the direct effect of smoking in non-COPD smokers showed decreases in the radiotracer (11C)DAA1106 [which binds to the microglial biomarker translocator proteins (TSPO)], compared to non-smokers ( Brody et al, 2017 ). However, Hillmer et al (2020) found no evidence of microglial activation in non-COPD smokers. These findings could be due to different radiotracer metabolism or bioavailability [(11C)DAA1106 and 11 CPBR28, respectively], or the use of different timeframes ( Hillmer et al, 2020 ).…”

“…However, Hillmer et al (2020) found no evidence of microglial activation in non-COPD smokers. These findings could be due to different radiotracer metabolism or bioavailability [(11C)DAA1106 and 11 CPBR28, respectively], or the use of different timeframes ( Hillmer et al, 2020 ). It is noteworthy that these studies only included non-COPD smoking participants, thus, caution must be taken when comparing to the current study.…”

Have (R)-[11C]PK11195 challengers fulfilled the promise? A scoping review of clinical TSPO PET studies

“…TSPO PET studies on addiction disorders include a single ( R )-[ 11 C]PK11195 report published in 2008 [ 135 ], and 10 more recent publications performed with 3 different challengers ([ 11 C]PBR28 [ 136 – 140 ], [ 11 C]DAA1106 [ 141 – 143 ], [ 18 F]FEPPA [ 144 , 145 ]). Results were highly dependent on i) addiction subtypes ( i.e.…”