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 to 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 towards diagnostic and therapeutic research and development.

中文翻译：

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对动物模型和帕金森病及相关疾病患者的 α-突触核蛋白病理进行成像

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。在这里，我们开发了一种小分子配体 C05-05，用于可视化活体受试者大脑中的 α-突触核蛋白沉积物。小鼠和狨猴模型的体内光学和正电子发射断层扫描 (PET) 成像表明，C05-05 捕获了原纤维生成沿神经通路的动态传播，随后这些结构被破坏。体外测定也证明了 ¹⁸ F-C05-05 与人脑组织中 α-突触核蛋白聚集体的高亲和力结合。值得注意的是，PET 可检测¹⁸与健康对照相比，PD 和 DLB 患者中脑中的 F-C05-05 信号增强，首次证明了这些疾病中 α-突触核蛋白病理的可视化。总的来说，我们提出了一种新的成像技术，为诊断和治疗研究和开发提供基于神经病理学的 PD 和相关疾病的转化评估。