Impact of Reference and Target Region Selection on Amyloid PET SUV Ratios in the Phase 1b PRIME Study of Aducanumab
Impact of Reference and Target Region Selection on Amyloid PET SUV Ratios in the Phase 1b PRIME Study of Aducanumab
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DOI：
10.2967/jnumed.118.209130
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发表时间：
2019-01-01
影响因子：
9.3
通讯作者：
Koeppe, Robert
中科院分区：
文献类型：
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作者：
Chiao, Ping;Bedell, Barry J.;Koeppe, Robert
SUV比率（SUVR）通常用于量化淀粉样蛋白-β PET中的示踪剂摄取。在本文中，我们使用正在进行的在前驱或轻度阿尔茨海默病患者中进行的aducanumab（BIIB 037）Ib期PRIME研究（NCT 01677572）的干预性数据，探索了靶点和参考感兴趣区（ROI）选择对SUVR效应量的影响。研究方法：使用整个小脑、小脑灰质、小脑白色物质、脑桥和皮质下白色物质作为参考区域，计算随机接受安慰剂和4种aducanumab剂量（1、3、6和10 mg/kg）的患者在基线（筛选）以及第26周和第54周时的florbetapir PET SUVR。除了预先指定的复合皮质目标ROI外，还将单个大脑皮质ROI作为目标进行评估。结果如下：在使用的参考区域中，皮质下白色物质、小脑白色物质和脑桥单独或组合产生最大的效应量。使用前扣带皮层作为目标ROI比使用复合皮层产生更大的效应量。SUVR计算不受脑容量随时间变化校正的影响。结论：仅在易于发生淀粉样斑块沉积的皮质区域中，使用aducanumab时始终观察到淀粉样蛋白PET SUVR的剂量和时间依赖性降低，无论使用的参考区域如何。这些数据支持以下假设：与aducanumab治疗相关的florbetapir SUVR反应是阿尔茨海默病患者淀粉样蛋白负荷特定剂量和时间依赖性降低的结果。
SUV ratios (SUVRs) are commonly used to quantify tracer uptake in amyloid-beta PET. Here, we explore the impact of target and reference region-of-interest (ROI) selection on SUVR effect sizes using interventional data from the ongoing phase 1b PRIME study (NCT01677572) of aducanumab (BIIB037) in patients with prodromal or mild Alzheimer disease. Methods: The florbetapir PET SUVR was calculated at baseline (screening) and at weeks 26 and 54 for patients randomized to receive placebo and each of 4 aducanumab doses (1, 3, 6, and 10 mg/kg) using the whole cerebellum, cerebellar gray matter, cerebellar white matter, pons, and subcortical white matter as reference regions. In addition to the prespecified composite cortex target ROI, individual cerebral cortical ROIs were assessed as targets. Results: Of the reference regions used, subcortical white matter, cerebellar white matter, and the pons, alone or in combination, generated the largest effect sizes. The use of the anterior cingulate cortex as a target ROI resulted in larger effect sizes than the use of the composite cortex. SUVR calculations were not affected by correction for brain volume changes over time. Conclusion: Dose-and time-dependent reductions in the amyloid PET SUVR were consistently observed with aducanumab only in cortical regions prone to amyloid plaque deposition, regardless of the reference region used. These data support the hypothesis that florbetapir SUVR responses associated with aducanumab treatment are a result of specific dose-and time-dependent reductions in the amyloid burden in patients with Alzheimer disease.