In Vivo Imaging of Post-Traumatic Cerebral Amyloid Deposition

描述（由申请人提供）：越来越多的证据表明，脑淀粉样蛋白β (Abeta)沉积在创伤性脑损伤（TBI）后迅速开始，是对轴突和氧化损伤的反应。我们的长期目标是验证正电子发射断层扫描（PET）成像与一种新型分子探针[18F]FDDNP的使用，在急性TBI的情况下，用于在体内观察β斑块。我们假设[18F]FDDNP结合的量与脑脊液中弥散β的浓度和患者预后相关。具体目的是：1)通过脑标本放射自显影和免疫组化证实[18F]FDDNP对脑损伤后脑内β沉积[18F]FDDNP摄取的特异性；2)通过[18F]FDDNP- pet成像评估脑内β斑块沉积与脑损伤后急性脑脊液β浓度之间的关系。[18F]FDDNP-PET已成功应用于阿尔茨海默病患者的淀粉样蛋白病理成像，可以早期诊断并提高对疾病的认识。我们相信，在大范围的TBI损伤严重程度中，PET可视化体内淀粉样蛋白沉积的能力将使我们首次能够评估发病率、时间过程和区域分布。更重要的是，它还可以提供一种无创工具来监测旨在减少淀粉样蛋白沉积（包括神经炎症调节剂）的治疗效果。简而言之，该研究设计需要使用FDDNP-PET研究一系列轻度至重度头部损伤患者在损伤后（3-10天）的急性损伤。该结果可能具有重要的公共卫生意义，因为提高对脑淀粉样蛋白沉积病理后果的理解可能导致改善TBI后预后的医学治疗。

DESCRIPTION (provided by applicant): Accumulating evidence suggests that cerebral amyloid beta (Abeta) deposition, which begins rapidly following traumatic brain injury (TBI), occurs in response to axonal and oxidative damage. Our long-term goal is to validate the use of positron emission tomography (PET) imaging with a novel molecular probe, [18F]FDDNP, for visualizing Abeta plaques, in vivo, in the setting of acute TBI. We hypothesize that the amount of [18F]FDDNP binding will correlate with both the concentration of diffusible Abeta in the cerebrospinal fluid and patient outcome. The Specific Aims are to 1) confirm the specificity of [18F]FDDNP for cerebral Abeta deposition [18F]FDDNP uptake following TBI using autoradiography and immunohistochemistry of brain specimens and, 2) determine the relationship between cerebral Abeta plaque deposition, assessed by [18F]FDDNP-PET imaging, and CSF Abeta concentration acutely following TBI. [18F]FDDNP-PET has been used successfully in imaging amyloid pathology in Alzheimer's disease patients, allowing early diagnosis and improved understanding of the disease. We believe that the ability to visualize amyloid deposition in vivo with PET, in a broad range of TBI injury severity, will allow us for the first time to assess the incidence, time course, and regional distribution. More importantly, it may also offer a noninvasive tool to monitor the efficacy of treatments aimed at decreasing amyloid deposition (including neuro-inflammation modulators). In brief, the research design entails studying a range of mild to severely head-injured patients acutely after injury (3-10 days) with FDDNP-PET. The results may have important public health implications in that improved understanding of the pathological consequences of cerebral amyloid deposition may lead to medical treatments that will improve outcome following TBI.