Molecular imaging of brain vesicular acetylcholine transporter provides a biomarker to explore cholinergic systems in humans. We aimed to characterize the distribution of, and optimize methods to quantify, the vesicular acetylcholine transporter–specific tracer (−)-(1-(8-(2-[¹⁸F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone ([¹⁸F]VAT) in the brain using PET. Methods: Fifty-two healthy participants aged 21–97 y had brain PET with [¹⁸F]VAT. [³H]VAT autoradiography identified brain areas devoid of specific binding in cortical white matter. PET image–based white matter reference region size, model start time, and duration were optimized for calculations of Logan nondisplaceable binding potential (BP_ND). Ten participants had 2 scans to determine test–retest variability. Finally, we analyzed age-dependent differences in participants. Results: [¹⁸F]VAT was widely distributed in the brain, with high striatal, thalamic, amygdala, hippocampal, cerebellar vermis, and regionally specific uptake in the cerebral cortex. [³H]VAT autoradiography–specific binding and PET [¹⁸F]VAT uptake were low in white matter. [¹⁸F]VAT SUVs in the white matter reference region correlated with age, requiring stringent erosion parameters. Logan BP_ND estimates stabilized using at least 40 min of data starting 25 min after injection. Test–retest variability had excellent reproducibility and reliability in repeat BP_ND calculations for 10 participants (putamen, 6.8%; r > 0.93). We observed age-dependent decreases in the caudate and putamen (multiple comparisons corrected) and in numerous cortical regions. Finally, we provide power tables to indicate potential mean differences that can be detected between 2 groups of participants. Conclusion: These results validate a reference region for BP_ND calculations and demonstrate the viability, reproducibility, and utility of using the [¹⁸F]VAT tracer in humans to quantify cholinergic pathways.

脑囊泡乙酰胆碱转运蛋白的分子成像为探索人类胆碱能系统提供了生物标志物。我们的目的是表征囊泡乙酰胆碱转运蛋白特异性示踪剂 (−)-(1-(8-(2-[ ¹⁸ F]氟乙氧基)-3-羟基-1,2,3 的分布并优化量化方法使用 PET 检测大脑中的 ,4-四氢萘-2-基)-哌啶-4-基)(4-氟苯基)甲酮 ([ ¹⁸ F]VAT)。方法： 52 名 21-97 岁的健康参与者接受了 [ ¹⁸ F]VAT 脑部 PET 检查。 [ ³ H]VAT放射自显影术确定了皮质白质中缺乏特异性结合的大脑区域。基于 PET 图像的白质参考区域大小、模型开始时间和持续时间针对 Logan 不可置换结合电位 (BP _ND ) 的计算进行了优化。 10 名参与者进行了 2 次扫描以确定重测变异性。最后，我们分析了参与者的年龄差异。结果： [ ¹⁸ F]VAT在大脑中分布广泛，纹状体、丘脑、杏仁核、海马、小脑蚓部的摄取较高，大脑皮层有区域特异性摄取。白质中的[ ³ H]VAT放射自显影-特异性结合和PET [ ¹⁸ F]VAT摄取较低。 [ ¹⁸ F]白质参考区域中的 VAT SUV 与年龄相关，需要严格的侵蚀参数。使用注射后 25 分钟开始的至少 40 分钟的数据，Logan BP _ND估计值稳定下来。在 10 名参与者的重复 BP _ND计算中，重测变异性具有出色的重现性和可靠性（壳核，6.8%； r > 0.93）。 我们观察到尾状核和壳核（多重比较已校正）以及许多皮质区域随年龄的减少。最后，我们提供功效表来指示两组参与者之间可以检测到的潜在平均差异。结论：这些结果验证了 BP _ND计算的参考区域，并证明了在人体中使用 [ ¹⁸ F]VAT 示踪剂来量化胆碱能通路的可行性、重现性和实用性。