Imaging the neuroimmune response to alcohol exposure in adolescent baboons: a TSPO PET study using [$^{18}$F]DPA-714

Abstract : The effects of acute alcohol exposure to the central nervous system are hypothesized to involve the innate immune system. The neuroimmune response to an initial and acute alcohol exposure was investigated using Translocator Protein 18 kDa (TSPO) PET imaging, a non-invasive marker of glial activation, in adolescent baboons. Three different alcoholnaive adolescent baboons (3-4 years old, 9 to 14 kg) underwent $^{18}$F-DPA-714 PET experiments before, during and 7-12 months after this initial alcohol exposure (0.7-1.0 g/L). The brain distribution of $^{18}$F-DPA-714 (V$_T$; in mL.cm$^{-3}$) was estimated in several brain regions using the Logan Plot analysis and the metabolite-corrected arterial input function. Compared to alcohol-naive animals (V$_{T\ brain}$ = 3.7 ± 0.7 mL.cm$^{-3}$), The regional V$_T$s of $^{18}$F-DPA-714 were significantly increased during alcohol exposure (V$_{T\ brain}$ = 7.2 ± 0.4 mL.cm$^{-3}$ ; p<0.001). Regional V$_T$s estimated several months after alcohol exposure (V$_{T\ brain}$ = 5.7 ± 1.4 mL.cm$^{-3}$) were lower (p<0.001) than those measured during alcohol exposure, but remained significantly higher (p<0.001) than in alcohol-naive animals. The acute and long-term effects of ethanol exposure were observed globally across all brain regions. Acute alcohol exposure increased the binding of $^{18}$F-DPA-714 to the brain in a nonhuman primate model of alcohol exposure that reflects the “binge drinking” situation in adolescent individuals. The effect persisted for several months, suggesting a “priming” of glial cell function after initial alcohol exposure.