Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
Department of Neurology, Skåne University Hospital, Lund, Sweden.
Nat Commun. 2023 Oct 27;14(1):6750. doi: 10.1038/s41467-023-42305-3.
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, [F]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 [F]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 [F]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，最终改善与α-突触核蛋白相关的疾病的治疗效果。在这里，我们展示了 PET 配体 [F] ACI-12589，使用放射自显影和放射性结合技术，在来自患有不同与α-突触核蛋白相关疾病（包括帕金森病（PD）和多系统萎缩（MSA））的患者的组织中，对病理性α-突触核蛋白显示出良好的体外亲和力和特异性。在初步的临床评估中，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。在体内，[F] ACI-12589 在 MSA 患者的小脑白质和小脑中间脑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区分了 MSA 患者与健康对照者和其他神经退行性疾病患者，包括其他突触核蛋白病患者。我们的结果表明，使用 [F] ACI-12589 PET 成像可以识别 MSA 中的α-突触核蛋白病理学，这可能会改善 MSA 的诊断工作流程，并允许检测新型靶向α-突触核蛋白的治疗药物在体内的药物靶点结合。
