Avid Radiopharmaceuticals, Philadelphia, PA, USA.
Lancet Neurol. 2012 Aug;11(8):669-78. doi: 10.1016/S1474-4422(12)70142-4. Epub 2012 Jun 28.
Results of previous studies have shown associations between PET imaging of amyloid plaques and amyloid-β pathology measured at autopsy. However, these studies were small and not designed to prospectively measure sensitivity or specificity of amyloid PET imaging against a reference standard. We therefore prospectively compared the sensitivity and specificity of amyloid PET imaging with neuropathology at autopsy.
This study was an extension of our previous imaging-to-autopsy study of participants recruited at 22 centres in the USA who had a life expectancy of less than 6 months at enrolment. Participants had autopsy within 2 years of PET imaging with florbetapir ((18)F). For one of the primary analyses, the interpretation of the florbetapir scans (majority interpretation of five nuclear medicine physicians, who classified each scan as amyloid positive or amyloid negative) was compared with amyloid pathology (assessed according to the Consortium to Establish a Registry for Alzheimer's Disease standards, and classed as amyloid positive for moderate or frequent plaques or amyloid negative for no or sparse plaques); correlation of the image analysis results with amyloid burden was tested as a coprimary endpoint. Correlation, sensitivity, and specificity analyses were also done in the subset of participants who had autopsy within 1 year of imaging as secondary endpoints. The study is registered with ClinicalTrials.gov, number NCT 01447719 (original study NCT 00857415).
We included 59 participants (aged 47-103 years; cognitive status ranging from normal to advanced dementia). The sensitivity and specificity of florbetapir PET imaging for detection of moderate to frequent plaques were 92% (36 of 39; 95% CI 78-98) and 100% (20 of 20; 80-100%), respectively, in people who had autopsy within 2 years of PET imaging, and 96% (27 of 28; 80-100%) and 100% (18 of 18; 78-100%), respectively, for those who had autopsy within 1 year. Amyloid assessed semiquantitatively with florbetapir PET was correlated with the post-mortem amyloid burden in the participants who had an autopsy within 2 years (Spearman ρ=0·76; p<0·0001) and within 12 months between imaging and autopsy (0·79; p<0·0001).
The results of this study validate the binary visual reading method approved in the USA for clinical use with florbetapir and suggest that florbetapir could be used to distinguish individuals with no or sparse amyloid plaques from those with moderate to frequent plaques. Additional research is needed to understand the prognostic implications of moderate to frequent plaque density.
Avid Radiopharmaceuticals.
先前的研究结果表明，正电子发射断层扫描（PET）成像的淀粉样斑块与尸检时测量的淀粉样-β 病理学之间存在关联。然而，这些研究规模较小，并非旨在前瞻性地测量淀粉样 PET 成像的敏感性或特异性与参考标准。因此，我们前瞻性地比较了淀粉样 PET 成像与尸检时的病理学结果。
这项研究是我们之前在美国 22 个中心招募参与者的影像学与尸检研究的延伸，这些参与者在入组时的预期寿命不到 6 个月。参与者在进行氟比他滨（(18)F）正电子发射断层扫描（PET）后的 2 年内接受了尸检。对于主要分析之一，对氟比他滨扫描的解释（五位核医学医师的多数解释，他们将每次扫描分类为淀粉样阳性或淀粉样阴性）与淀粉样病理学（根据阿尔茨海默病研究协会标准进行评估，并分为中度或频繁斑块的淀粉样阳性或无或稀疏斑块的淀粉样阴性）进行了比较；将图像分析结果与淀粉样蛋白负荷的相关性作为共同主要终点进行了测试。在作为次要终点的影像学检查后 1 年内接受尸检的参与者亚组中，也进行了相关性、敏感性和特异性分析。该研究在 ClinicalTrials.gov 注册，编号为 NCT 01447719（原始研究 NCT 00857415）。
我们纳入了 59 名参与者（年龄 47-103 岁；认知状态从正常到重度痴呆）。在影像学检查后 2 年内接受尸检的参与者中，氟比他滨 PET 成像检测中度至频繁斑块的敏感性和特异性分别为 92%（36/39；95%CI 78-98）和 100%（20/20；80-100%），在影像学检查后 1 年内接受尸检的参与者中，敏感性和特异性分别为 96%（27/28；80-100%）和 100%（18/18；78-100%）。在 2 年内接受尸检的参与者中，氟比他滨 PET 半定量评估的淀粉样蛋白与尸检后的淀粉样蛋白负荷呈正相关（Spearman ρ=0·76；p<0·0001），与影像学检查后 12 个月内的淀粉样蛋白负荷也呈正相关（0·79；p<0·0001）。
这项研究的结果验证了美国批准用于临床使用氟比他滨的二元视觉阅读方法，并表明氟比他滨可用于区分无或稀疏淀粉样斑块与中度至频繁斑块的个体。需要进一步研究来了解中度至频繁斑块密度的预后意义。
艾维德放射性药物公司。
