There are limited validated biomarkers in Parkinson disease (PD) which substantially hinders the ability to monitor disease progression and consequently measure the efficacy of disease-modifying treatments. Imaging biomarkers, such as vesicular monoamine transporter type 2 (VMAT2) PET, enable enhanced diagnostic accuracy and detect early neurodegenerative changes associated with prodromal PD. This study sought to assess whether ¹⁸F-AV-133 VMAT2 PET is sensitive enough to monitor and quantify disease progression over a 2-year window.

¹⁸F-AV-133 PET scans were performed on participants with PD and REM sleep behavior disorder (RBD) and neurologic controls (NC). All participants were scanned twice ~26 months apart. Regional tracer retention was calculated with a primary visual cortex reference region and expressed as the standard uptake volume ratio. Regions of interest included caudate, anterior, and posterior putamen. At the time of scanning, participants underwent clinical evaluation including UPDRS_MOTOR test, Sniffin’ Sticks, and Hospital Anxiety and Depression Score.

Over the 26-month interval, a significant decline in PET signal was observed in all 3 regions in participants with PD (N = 26) compared with NC (N = 12), consistent with a decrease in VMAT2 level and ongoing neurodegeneration. Imaging trajectory calculations suggest that the neurodegeneration in PD occurs over ~33 years [CI: 27.2–39.5], with ~10.5 years [CI: 9.1–11.3] of degeneration in the posterior putamen before it becomes detectable on a VMAT2 PET scan, a further ~6.5 years [CI: 1.6–12.7] until symptom onset, and a further ~3 years [CI: 0.3–8.7] until clinical diagnosis.

Over a 2-year period, ¹⁸F-AV-133 VMAT2 PET was able to detect progression of nigrostriatal degeneration in participants with PD, and it represents a sensitive tool to identify individuals at risk of progression to PD, which are currently lacking using clinical readouts. Trajectory models propose that there is nigrostriatal degeneration occurring for 20 years before clinical diagnosis. These data demonstrate that VMAT2 PET provides a sensitive measure to monitor neurodegenerative progression of PD which has implications for PD diagnostics and subsequently clinical trial patient stratification and monitoring.

This study provides Class IV evidence that VMAT2 PET can detect patients with Parkinson disease and quantify progression over a 2-year window.

帕金森病 (PD) 中经过验证的生物标志物有限，这极大地阻碍了监测疾病进展并进而衡量疾病缓解治疗效果的能力。成像生物标志物，例如 2 型囊泡单胺转运蛋白 (VMAT2) PET，可以提高诊断准确性并检测与前驱 PD 相关的早期神经退行性变化。本研究旨在评估¹⁸ F-AV-133 VMAT2 PET 是否足够敏感，能够监测和量化 2 年窗口内的疾病进展。

对患有 PD 和 REM 睡眠行为障碍 (RBD) 以及神经系统对照 (NC) 的参与者进行了^{18 次F-AV-133 PET 扫描。}所有参与者均接受两次扫描，间隔约 26 个月。使用初级视觉皮层参考区域计算区域示踪剂保留并表示为标准摄取体积比。感兴趣的区域包括尾状核、前壳核和后壳核。在扫描时，参与者接受了临床评估，包括 UPDRS _MOTOR测试、Sniffin' Sticks 和医院焦虑和抑郁评分。

在 26 个月的时间间隔内，与 NC (N = 12) 相比，PD (N = 26) 参与者的所有 3 个区域的 PET 信号均显着下降，这与 VMAT2 水平下降和持续的神经退行性疾病一致。影像轨迹计算表明，PD 中的神经变性发生时间约为 33 年 [CI：27.2–39.5]，后壳核变性约 10.5 年 [CI：9.1–11.3]，然后才能通过 VMAT2 PET 扫描检测到。大约 6.5 年 [CI：1.6–12.7] 直到症状出现，再大约 3 年 [CI：0.3–8.7] 直到临床诊断。

在 2 年的时间内，¹⁸ F-AV-133 VMAT2 PET 能够检测 PD 参与者的黑质纹状体变性进展情况，并且它是识别有进展为 PD 风险的个体的敏感工具，目前临床上缺乏这种工具。读数。轨迹模型提出，在临床诊断之前，黑质纹状体变性已发生 20 年。这些数据表明，VMAT2 PET 提供了一种敏感的方法来监测 PD 的神经退行性进展，这对 PD 诊断以及随后的临床试验患者分层和监测具有重要意义。

这项研究提供了 IV 级证据，证明 VMAT2 PET 可以检测帕金森病患者并量化 2 年窗口内的进展情况。