Abstract：
Deposition of α-synuclein fibrils is implicated in Parkinson\'s disease (PD) and dementia with Lewy bodies (DLB), while in vivo detection of α-synuclein pathologies in these illnesses has been challenging. Here, we have developed a small-molecule ligand, C05-05, for visualizing α-synuclein deposits in the brains of living subjects. In vivo optical and positron emission tomography (PET) imaging of mouse and marmoset models demonstrated that C05-05 captured a dynamic propagation of fibrillogenesis along neural pathways, followed by disruptions of these structures. High-affinity binding of 18F-C05-05 to α-synuclein aggregates in human brain tissues was also proven by in vitro assays. Notably, PET-detectable 18F-C05-05 signals were intensified in the midbrains of PD and DLB patients as compared with healthy controls, providing the first demonstration of visualizing α-synuclein pathologies in these illnesses. Collectively, we propose a new imaging technology offering neuropathology-based translational assessments of PD and allied disorders toward diagnostic and therapeutic research and development.
摘要：
α-突触核蛋白原纤维的沉积与帕金森病（PD）和路易体痴呆（DLB）有关，而这些疾病中α-突触核蛋白病理的体内检测一直具有挑战性。这里,我们开发了一种小分子配体，C05-05,用于可视化活体受试者脑中的α-突触核蛋白沉积物。小鼠和melmoset模型的体内光学和正电子发射断层扫描（PET）成像表明，C05-05捕获了纤维形成沿神经通路的动态传播，其次是这些结构的破坏。18F-C05-05与人脑组织中的α-突触核蛋白聚集体的高亲和力结合也通过体外测定得到证实。值得注意的是,与健康对照相比，PD和DLB患者的中脑中PET可检测的18F-C05-05信号增强，提供了在这些疾病中可视化α-突触核蛋白病理的第一个演示。总的来说，我们提出了一种新的成像技术,为PD和相关疾病的诊断和治疗研究和开发提供基于神经病理学的转化评估.
