Raval Nakul R, Smart Kelly, Angarita Gustavo A, Miller Rachel, Huang Yiyun, Krystal John H, Carson Richard E, Cosgrove Kelly P, O'Malley Stephanie S, Hillmer Ansel T
Yale PET Center, Yale University, New Haven, Connecticut, USA.
Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.
Addict Biol. 2025 May;30(5):e70031. doi: 10.1111/adb.70031.
Alcohol consumption at clinically relevant doses alters brain glutamate release. However, few techniques exist to measure these changes in humans. The metabotropic glutamate receptor 5 (mGluR5) PET radioligand [C]ABP688 is sensitive to acute alcohol in rodents, possibly mediated by alcohol effects on glutamate release. This study aimed to determine the sensitivity of [C]ABP688 PET to an acute alcohol challenge in humans.
Eight social drinkers (25-42 years; 5 females) with a recent drinking occasion achieving a blood alcohol level (BAL) > 80 mg/dL were recruited. All participants underwent a 90-min dynamic baseline [C]ABP688 PET scan. Two weeks later (range: 7-29 days), participants completed an oral laboratory alcohol challenge over 30 min, targeting a BAL of 60 mg/dL. Immediately after the challenge, a second [C]ABP688 PET scan was performed. Non-displaceable binding potential (BP; indicative of mGluR5 availability) and R (indicative of relative blood flow) were estimated using the simplified reference tissue model with the cerebellum as the reference region. Blood samples were taken throughout the scanning procedure to measure the BAL.
Seven participants (4 females) completed the study. The mean peak BAL achieved was 61 ± 18 mg/dL. Acute alcohol significantly decreased [C]ABP688 BP, F(1, 42) = 17.05, p < 0.001, Cohen's d = 0.32-0.60, and increased [C]ABP688 R, F(1, 42) = 6.67, p = 0.013, Cohen's d = 0.32-0.48, across brain regions. Exploratory analysis showed a positive relationship between alcohol-induced % change in [C]ABP688 R in cortical regions and peak BAL (Spearman rho = 0.78 [frontal cortex] and 0.85 [temporal cortex] = 0.024 and 0.011).
This proof-of-concept study demonstrates that [C]ABP688 PET imaging is sensitive to the effects of acute alcohol consumption. The observed decrease in mGluR5 availability aligns with preclinical data potentially indicating acute increased extracellular glutamate concentrations following ethanol dosing. This imaging tool could be useful for future investigations into the acute effects of alcohol on the brain during abstinence and withdrawal.
临床相关剂量的酒精摄入会改变大脑谷氨酸的释放。然而，在人类中测量这些变化的技术很少。代谢型谷氨酸受体5（mGluR5）PET放射性配体[C]ABP688对啮齿动物体内的急性酒精敏感，这可能是由酒精对谷氨酸释放的影响介导的。本研究旨在确定[C]ABP688 PET对人类急性酒精激发试验的敏感性。
招募了8名近期饮酒后血液酒精浓度（BAL）>80mg/dL的社交饮酒者（25 - 42岁；5名女性）。所有参与者均接受了90分钟的动态基线[C]ABP688 PET扫描。两周后（范围：7 - 29天），参与者在30分钟内完成了一次口服实验室酒精激发试验，目标BAL为60mg/dL。激发试验后立即进行第二次[C]ABP688 PET扫描。使用以小脑为参考区域的简化参考组织模型估计非置换结合潜能（BP；指示mGluR5的可用性）和R（指示相对血流）。在整个扫描过程中采集血样以测量BAL。
7名参与者（4名女性）完成了研究。达到的平均峰值BAL为61±18mg/dL。急性酒精显著降低了[C]ABP688 BP，F(1, 42) = 17.05，p < 0.001，Cohen's d = 0.32 - 0.60，并增加了[C]ABP688 R，F(1, 42) = 6.67，p = 0.013，Cohen's d = 0.32 - 0.48， across brain regions. Exploratory analysis showed a positive relationship between alcohol-induced % change in [C]ABP688 R in cortical regions and peak BAL (Spearman rho = 0.78 [frontal cortex] and 0.85 [temporal cortex] = 0.024 and 0.011).
这项概念验证研究表明，[C]ABP688 PET成像对急性酒精摄入的影响敏感。观察到的mGluR5可用性降低与临床前数据一致，这可能表明乙醇给药后细胞外谷氨酸浓度急性升高。这种成像工具可能有助于未来对戒酒和戒断期间酒精对大脑急性影响的研究。
