A positron emission tomography (PET) tracer detecting α-synuclein pathology will improve the diagnosis, and ultimately the treatment of α-synuclein-related diseases. Here we show that the PET ligand, [¹⁸F]ACI-12589, displays good in vitro affinity and specificity for pathological α-synuclein in tissues from patients with different α-synuclein-related disorders including Parkinson’s disease (PD) and Multiple-System Atrophy (MSA) using autoradiography and radiobinding techniques. In the initial clinical evaluation we include 23 participants with α-synuclein related disorders, 11 with other neurodegenerative disorders and eight controls. In vivo [¹⁸F]ACI-12589 demonstrates clear binding in the cerebellar white matter and middle cerebellar peduncles of MSA patients, regions known to be highly affected by α-synuclein pathology, but shows limited binding in PD. The binding statistically separates MSA patients from healthy controls and subjects with other neurodegenerative disorders, including other synucleinopathies. Our results indicate that α-synuclein pathology in MSA can be identified using [¹⁸F]ACI-12589 PET imaging, potentially improving the diagnostic work-up of MSA and allowing for detection of drug target engagement in vivo of novel α-synuclein targeting therapies.

正电子发射断层扫描 (PET) 示踪剂检测 α-突触核蛋白病理学将改善诊断，并最终改善 α-突触核蛋白相关疾病的治疗。在此，我们表明，PET 配体 [ ¹⁸ F]ACI-12589 对患有不同 α-突触核蛋白相关疾病（包括帕金森病 (PD) 和多系统疾病）的患者组织中的病理性 α-突触核蛋白表现出良好的体外亲和力和特异性。使用放射自显影和放射结合技术进行萎缩（MSA）。在最初的临床评估中，我们纳入了 23 名患有 α-突触核蛋白相关疾病的参与者、11 名患有其他神经退行性疾病的参与者和 8 名对照者。体内 [ ¹⁸ F]ACI-12589 在 MSA 患者的小脑白质和小脑中脚中显示出明显的结合，这些区域已知受 α-突触核蛋白病理学的高度影响，但在 PD 中显示出有限的结合。这种结合在统计学上将 MSA 患者与健康对照组和患有其他神经退行性疾病（包括其他突触核蛋白病）的受试者区分开来。我们的结果表明，可以使用 [ ¹⁸ F]ACI-12589 PET 成像来识别 MSA 中的 α-突触核蛋白病理，这可能会改善 MSA 的诊断工作，并允许检测新型 α-突触核蛋白靶向疗法的体内药物靶点参与情况。