PT - JOURNAL ARTICLE AU - Corinde Wiers AU - Sung Won Kim AU - Ehsan Shokri Kojori AU - Leandro Vendruscolo AU - Min Guo AU - Jeih-San Liow AU - Elsa Lindgren AU - Gregg Miller AU - Ryan Tyler AU - Clara Freeman AU - Amna Zehra AU - Veronica Ramirez AU - Yeon Joo Jang AU - Sukru Demiral AU - Dardo Tomasi AU - Nancy Diazgranados AU - Victor Pike AU - Robert Innis AU - Gene-Jack Wang AU - George Koob AU - Nora Volkow TI - Neuroinflammation in alcoholism using [<sup>11</sup>C]PBR28: from rat to human DP - 2017 May 01 TA - Journal of Nuclear Medicine PG - 137--137 VI - 58 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/58/supplement_1/137.short 4100 - http://jnm.snmjournals.org/content/58/supplement_1/137.full SO - J Nucl Med2017 May 01; 58 AB - 137Objectives: There is preclinical evidence that chronic alcohol exposure leads to brain neuroinflammation, which may contribute to alcohol-induced cognitive impairment. To assess if alcoholism is associated with neuroinflammation in the brain, we compared the binding of [11C]PBR 28, a TSPO ligand that serves as marker for microglial activation, using PET in participants with alcohol use disorder (AUD) and in healthy controls (HC), and in a rat model of alcoholism.Methods: Fourteen patients with AUD (age=47±10SD), 3 female) and eight HC (age=46±9, 1 female) underwent a [11C]PBR 28 PET scan and structural MRI. Groups were matched for age (p=0.8), sex (p=0.6), IQ (p=0.1), BMI (p=0.4), and TSPO genotype (AUD: 9 high, 5 mixed; HC: 6 high; 2 mixed-affinity binders; p=0.6). AUD patients drank an average of 63±39 alcoholic drinks per week (HC: 1±2drink per week; p&lt;0.0001), and 11842±845kg lifetime (HC: 29±45 kg lifetime). AUD had a last drinking episode within 7 days of the PET scan. [11C]PBR 28 PET scans were also performed in Wistar rats that were chronically exposed to high doses of alcohol (blood level alcohol=196 mg/dL) for 1.5-2.5 months (n=10) and in nondependent control rats (n=10). Further, rat brains were harvested after each PET scan for in vitro autoradiography using [3H]PK 11195, which is also a ligand for TSPO.Results: Contrary to our hypothesis, AUD patients showed decreased [11C]PBR 28 standardized uptake values (SUV) compared to HC in all regions of interest (ROIs): whole brain (p=0.04), white matter (p=0.04), gray matter (p=0.033), thalamus (p=0.049, cingulum (p=0.048), and cerebellum (p=0.026). Moreover, SUV values in all ROIs correlated negatively with life-time drinking in AUD and HC groups (all p&lt;0.01), but not with age. Mean total distribution volumes acquired by the 2-tissue compartment model were also consistently lower in AUD compared to HC. Statistical voxel-wise parametric mapping (SPM) analysis on SUVr (SUV normalized by whole brain SUV), however, showed evidence of increased [11C]PBR 28 uptake in white matter in AUD versus controls (peak MNI coordinates: [15, 56, 19], t=3.76, p&lt;.001 cluster-corrected). Alcohol-exposed rats also showed decreased whole brain [11C]PBR 28 SUV compared to controls in vivo (averaged in 30-60 min, F=6.6, p&lt;.05). In addition, preliminary ex vivo autoradiography results showed a 38±14% decrease of [3H]PK 11195 specific binding in alcohol-exposed rat brains compared to control brains (6 sections, n=3 vs n=3).Conclusion: Here we show that TSPO expression may decrease after chronic alcohol consumption, as evidenced by decreased brain [11C]PBR 28 uptake in humans and in rats in vivo; and of reduced [3H]PK 11195 binding in rats ex vivo. Mechanisms underlying the overall reduction of TSPO in the brain of alcoholics requires further investigation. However, after normalization for the overall reduced binding of [11C]PBR 28 in the brain, our results provide evidence of increased relative binding in white matter, which could reflect its greater vulnerability to neuroinflammatory changes associated with chronic alcohol exposure. Research Support: Supported by NIH IRP (Y1AA3009)