Effect of overnight smoking abstinence on a marker for microglial activation: a [11C]DAA1106 positron emission tomography study

Abstract

Rationale: Microglia are the main immune cells in the central nervous system and participate in neuroinflammation. When activated, microglia express increased levels of the translocator protein 18 kDa (TSPO), thereby making TSPO availability a marker for neuroinflammation. Using positron emission tomography (PET) scanning, our group recently demonstrated that smokers in the satiated state had 16.8% less binding of the radiotracer [¹¹C]DAA1106 (a radioligand for TSPO) in the brain than nonsmokers.

Objectives: We sought to determine the effect of overnight smoking abstinence on [¹¹C]DAA1106 binding in the brain.

Methods: Forty participants (22 smokers and 18 nonsmokers) completed the study (at one of two sites) and had usable data, which included images from a dynamic [¹¹C]DAA1106 PET scanning session (with smokers having been abstinent for 17.9 ± 2.3 h) and a blood sample for TSPO genotyping. Whole brain standardized uptake values (SUVs) were determined, and analysis of variance was performed, with group (overnight abstinent smoker vs. nonsmoker), site, and TSPO genotype as factors, thereby controlling for site and genotype.

Results: Overnight abstinent smokers had lower whole brain SUVs (by 15.5 and 17.0% for the two study sites) than nonsmokers (ANCOVA, P = 0.004). The groups did not significantly differ in injected radiotracer dose or body weight, which were used to calculate SUV.

Conclusions: These results in overnight abstinent smokers are similar to those in satiated smokers, indicating that chronic cigarette smoking leads to global impairment of microglial activation which persists into early abstinence. Other explanations for study results, such as smoking leading to reduced numbers of microglia or smokers having more rapid metabolism of the radiotracer than nonsmokers, are also possible.

Keywords: Cigarette withdrawal; Magnetic resonance imaging; Microglial activation; Neuroinflammation; Positron emission tomography; Tobacco dependence; [11C]DAA1106.

Figure 1:

Flow diagram showing the number of potential and actual participants at each step of the study, including reasons for potential participants being screened out of participation.

Figure 2:

Scatterplot showing inverse correlation (−0.74, P=0.02) between whole brain standardized uptake values and smokers’ ratings of depth of inhalation (for study smokers who filled out this questionnaire). The correlation value controlled for translocator protein genotype (high versus medium affinity).