Using 18F-AV-133 VMAT2 PET Imaging to Monitor Progressive Nigrostriatal Degeneration in Parkinson Disease
Using 18F-AV-133 VMAT2 PET Imaging to Monitor Progressive Nigrostriatal Degeneration in Parkinson Disease
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DOI：
10.1212/wnl.0000000000207748
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发表时间：
2023-11-28
期刊：
影响因子：
9.9
通讯作者：
Rowe, Christopher
中科院分区：
文献类型：
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作者：
Beauchamp, Leah C.;Dore, Vincent;Rowe, Christopher
背景帕金森病(Parkinson‘s Disease，PD)中有效的生物标志物有限，这严重阻碍了监测疾病进展的能力，从而影响了疾病调整治疗的有效性。成像生物标志物，如VMAT2PET，能够提高诊断的准确性，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F-18-AV-133 VMAT2 PET是否足够灵敏，可以在两年的时间窗口内监测和量化疾病的进展。方法对患有PD和REM睡眠行为障碍(RBD)和神经控制(NC)的参与者进行F-18-AV-133 PET扫描。所有参与者都接受了两次扫描，相隔26个月。用初级视觉皮质参考区计算区域示踪剂保留量，并用标准摄取体积比表示。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UPDRSMOTOR测试、Sniffin棍棒和医院焦虑和抑郁评分。结果在26个月的时间间隔内，PD患者(N=26)的三个区域以及RBD患者(N=11)的后壳核的PET信号与NC(N=12)相比显著下降，与VMAT2水平的下降和正在进行的神经变性一致。影像轨迹计算表明，帕金森病患者的神经退行性变发生的时间类似于33年[CI：27.2，39.5]，在VMAT2 PET扫描中可检测到后壳核的变性类似于10.5年[CI：9.1-11.3]，进一步类似于症状出现前的6.5年[CI：1.6，12.7]，以及临床诊断前的3年[CI：0.3，8.7]。F-18-AV-133 VMAT2 PET能够检测帕金森病患者黑质纹状体变性的进展，是识别进展为帕金森病风险个体的敏感工具，目前临床读数缺乏这种工具。轨迹模型表明在临床诊断前存在20年的黑质纹状体退行性变。这些数据表明，VMAT2 PET为监测帕金森病的神经退行性进展提供了一种灵敏的方法，这对帕金森病的诊断和随后的临床试验患者分层和监测具有重要意义。证据分类本研究提供了IV类证据，表明VMAT2 PET可以检测帕金森病患者并量化两年窗口内的进展。
BackgroundThere are limited validated biomarkers in Parkinson's disease (PD) which substantially hinders the ability to monitor disease progression and consequently measure the efficacy of disease-modifying treatments. Imaging biomarkers, such as VMAT2 PET, enable enhanced diagnostic accuracy, and detect early neurodegenerative changes associated with prodromal PD. This study sought to assess whether F-18-AV-133 VMAT2 PET is sensitive enough to monitor and quantify disease progression over a two-year window.Methods F-18-AV-133 PET scans were performed on participants with PD and REM sleep behavior disorder (RBD) and neurological controls (NC). All participants were scanned twice similar to 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 UPDRSMOTOR test, Sniffin' Sticks, and Hospital Anxiety and Depression Score.Results Over the 26-month interval a significant decline in PET signal was observed in all three regions in participants with PD (N=26) and in the posterior putamen in participants with RBD (N=11) compared to NC (N=12), consistent with a decrease in VMAT2 level and ongoing neurodegeneration. Imaging trajectory calculations suggest the neurodegeneration in PD occurs over similar to 33 years [CI: 27.2, 39.5], with similar to 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 similar to 6.5 years [CI: 1.6,12.7] until symptom onset, and a further similar to 3 years [CI: 0.3,8.7] until clinical diagnosis.Discussion Over a two-year period, F-18-AV-133 VMAT2 PET was able to detect progression of nigrostriatal degeneration in participants with PD and 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.Classification of evidenceThis study provides Class IV evidence that VMAT2 PET can detect patients with Parkinson Disease and quantify progression over a two-year window.