1] Division of Nuclear Medicine and Molecular Imaging, Weill Cornell Medical College, New York, NY, USA [2] Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
Neuropsychopharmacology. 2013 Oct;38(11):2170-8. doi: 10.1038/npp.2013.114. Epub 2013 May 10.
Cocaine addiction is a major problem for which there is no approved pharmacotherapy. We have developed a vaccine to cocaine (dAd5GNE), based on the cocaine analog GNE linked to the capsid proteins of a serotype 5 adenovirus, designed to evoke anti-cocaine antibodies that sequester cocaine in the blood, preventing access to the CNS. To assess the efficacy of dAd5GNE in a large animal model, positron emission tomography (PET) and the radiotracer [(11)C]PE2I were used to measure cocaine occupancy of the dopamine transporter (DAT) in nonhuman primates. Repeat administration of dAd5GNE induced high anti-cocaine titers. Before vaccination, cocaine displaced PE2I from DAT in the caudate and putamen, resulting in 62±4% cocaine occupancy. In contrast, dAd5GNE-vaccinated animals showed reduced cocaine occupancy such that when anti-cocaine titers were >4 × 10(5), the cocaine occupancy was reduced to levels of <20%, significantly below the 47% threshold required to evoke the subjective 'high' reported in humans.
可卡因成瘾是一个重大问题，目前尚无经过批准的药物疗法。我们开发了一种可卡因疫苗（dAd5GNE），基于与血清型 5 腺病毒衣壳蛋白相连的可卡因类似物 GNE，旨在引发抗可卡因抗体，将可卡因在血液中隔离，防止其进入中枢神经系统。为了在大型动物模型中评估 dAd5GNE 的疗效，我们使用正电子发射断层扫描（PET）和放射性示踪剂 [(11)C]PE2I 来测量可卡因在非人类灵长类动物多巴胺转运体（DAT）中的占据率。重复给予 dAd5GNE 可诱导高抗可卡因滴度。在接种疫苗之前，可卡因会从尾状核和壳核中的 DAT 上置换 PE2I，导致 62±4%的可卡因占据率。相比之下，dAd5GNE 疫苗接种的动物显示可卡因占据率降低，以至于当抗可卡因滴度 >4×10(5)时，可卡因占据率降低至 <20%，显著低于在人类中引发报告的主观“高”所需的 47%阈值。
