Neuroscience Research Institute, Gachon University of Medicine and Science, 1197 Guwol-dong, Namdong-gu, Incheon 405-760, Republic of Korea.
Neuroimage. 2010 Aug 15;52(2):488-96. doi: 10.1016/j.neuroimage.2010.04.013. Epub 2010 Apr 10.
Beta amyloid plaques, neurofibrillary tangles, and impaired glucose metabolism are among the most prevalent pathological characteristics of Alzheimer's disease (AD). However, separate visualization of these three AD-related pathologies in living humans has not been conducted. Here, we show that positron emission tomography (PET) imaging using the three radiotracers (11)C-Pittsburgh compound B (PIB), 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile (FDDNP), and 2-[18F]fluoro-2-deoxy-d-glucose (FDG), in the same subjects, with and without AD, can provide valuable information on the pathological patterns of the distribution of tracers for amyloid plaque, neurofibrillary tangle, and glucose hypometabolism in AD. Voxel-based analysis of PIB-PET in patients with AD compared with normal control subjects showed that patients with AD have highly significant PIB retention in brain regions known to have high amyloid plaque deposition (e.g., frontal, parietal, temporal, and posterior cingulate/precuneus cortices). In contrast, voxel-based analysis of FDDNP-PET showed significantly high FDDNP binding in some brain regions known to have high tangle accumulation in patients with AD compared with age-matched normal subjects (e.g., entorhinal cortex, inferior temporal gyrus, and secondary visual cortex). In addition, because FDDNP binds both plaques and tangles but PIB binds plaques specifically, we examined subtracted PET data (FDDNP minus PIB) acquired from the same patients with AD using an SPM analysis. We found that the hippocampal formation was the most significant brain region in the voxel mapping of FDDNP minus PIB in the same patients with AD. Voxel-based analysis of FDG-PET in the same subjects revealed that brain regions with glucose hypometabolism in patients with AD overlap with regions of high PIB binding. In conclusion, PET imaging using these three radiotracers in the same subjects may contribute toward developing and testing disease-modifying drugs targeting amyloid pathology, tau pathology, and/or energy metabolism.
β淀粉样斑块、神经纤维缠结和葡萄糖代谢受损是阿尔茨海默病（AD）最常见的病理特征之一。然而，在活体人类中分别观察这三种 AD 相关病理学尚未进行。在这里，我们展示了使用三种放射性示踪剂（11C-Pittsburgh 化合物 B（PIB）、2-（1-{6-[(2-（18）F-氟乙基）（甲基）氨基]-2-萘基}亚乙基）丙二腈（FDDNP）和 2-[18F]氟-2-脱氧-D-葡萄糖（FDG），在相同的受试者中进行正电子发射断层扫描（PET）成像，无论是有无 AD，都可以为 AD 中淀粉样斑块、神经纤维缠结和葡萄糖代谢低下的示踪剂分布的病理模式提供有价值的信息。与正常对照组相比，AD 患者 PIB-PET 的基于体素分析显示，AD 患者的大脑区域具有高度显著的 PIB 保留，这些区域已知具有高淀粉样斑块沉积（例如，额、顶、颞和后扣带回/楔前叶皮质）。相比之下，基于体素的 FDDNP-PET 分析显示，与年龄匹配的正常受试者相比，AD 患者的一些已知具有高缠结积累的大脑区域具有显著高的 FDDNP 结合（例如，内嗅皮质、下颞叶和次级视觉皮层）。此外，由于 FDDNP 结合斑块和缠结，但 PIB 特异性结合斑块，我们使用 SPM 分析检查了从相同 AD 患者获得的 FDDNP 减去 PIB 的减去 PET 数据。我们发现，在相同 AD 患者的 FDDNP 减去 PIB 体素映射中，海马结构是最显著的大脑区域。相同受试者的 FDG-PET 基于体素分析显示，AD 患者的葡萄糖代谢低下的大脑区域与 PIB 结合高的区域重叠。总之，在相同的受试者中使用这三种放射性示踪剂进行 PET 成像可能有助于开发和测试针对淀粉样蛋白病理学、tau 病理学和/或能量代谢的疾病修饰药物。
