Preliminary Evidence for [¹¹C]PBR28 Sensitivity to Alcohol Challenge in Human Brain

Objectives: Alcohol elicits complex effects on the brain’s immune system, however, limited in vivo tools exist to study these phenomena in people. Positron emission tomography (PET) imaging of the 18-kDa translocator protein (TSPO) provides a useful biomarker that is sensitive to dynamic changes in the immune system. For example, the robust immune stimulus endotoxin increases [¹¹C]PBR28 V_T by 40-50% in human brain (Sandiego et al., 2015). The goal of this work was to determine whether [¹¹C]PBR28 PET imaging is sensitive to acute immune effects elicited by an oral alcohol challenge.

Methods: Study participants were six people (4M, 2F; Age 21-31) who reported recent drinking experience consistent with a binge alcohol event. Baseline dynamic [¹¹C]PBR28 PET scans were acquired in the morning, followed by a standardized lunch. Subjects then consumed an alcohol dose adjusted by age, sex, and weight, designed to achieve blood alcohol concentrations (BAC) of 80 mg/dL over 90 min. Following a 60 min rest period, a second post-alcohol [¹¹C]PBR28 PET scan was acquired. Arterial blood samples were acquired at 30 min intervals to measure BAC. Dynamic PET data were acquired with a Siemens Biograph mCT PET/CT scanner for at least 90 min following injection of 427±142 MBq [¹¹C]PBR28. Arterial blood samples were collected to measure the metabolite-corrected input function. Multilinear analysis was used to estimate [¹¹C]PBR28 distribution volumes (V_T) in 9 brain regions.

Results: In five subjects with available BAC measures, peak levels of 89±21 mg/dL were achieved 90-120 min after initiation of the alcohol session. BAC levels were, on average, 59±14 mg/dL during the PET imaging sessions. Averaged across all subjects and brain regions, the alcohol challenge increased [¹¹C]PBR28 V_T by 19% (range, 3%-38%). There was no initial evidence for regional patterns in alcohol’s effects on [¹¹C]PBR28 V_T.

Conclusions: These preliminary data suggest that [¹¹C]PBR28 V_T is sensitive to an oral alcohol challenge in people. Data collection is ongoing to confirm these results in a larger cohort. This imaging approach shows promise for future studies of alcohol-related disorders. References: Sandiego, C.M., et al., 2015. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proc. Nat. Acad. Sci. 112, 12468-12473.