阿尔茨海默病患者和健康对照者用氟比苯（18F）行脑淀粉样蛋白 PET：一项多中心 2 期诊断研究。

Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study.

机构信息

Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.

出版信息

Lancet Neurol. 2011 May;10(5):424-35. doi: 10.1016/S1474-4422(11)70077-1. Epub 2011 Apr 8.

DOI:10.1016/S1474-4422(11)70077-1

PMID:21481640

Abstract

BACKGROUND

Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer's disease. Florbetaben (¹⁸F) is a promising ¹⁸F-labelled amyloid-β-targeted PET tracer in clinical development. We aimed to assess the sensitivity and specificity of florbetaben (¹⁸F) PET in discriminating between patients with probable Alzheimer's disease and elderly healthy controls.

METHODS

We did a multicentre, open-label, non-randomised phase 2 study in 18 centres in Australia, Germany, Switzerland, and the USA. Imaging with florbetaben (¹⁸F) PET was done on patients with probable Alzheimer's disease (age 55 years or older, mini-mental state examination [MMSE] score=18-26, clinical dementia rating [CDR]=0·5-2·0) and age-matched healthy controls (MMSE ≥ 28, CDR=0). Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90-110 min post-injection. PET images were assessed visually by three readers masked to the clinical diagnosis and all other clinical findings, and quantitatively by use of pre-established brain volumes of interest to obtain standard uptake value ratios (SUVRs), taking the cerebellar cortex as the reference region. This study is registered with ClinicalTrials.gov, number NCT00750282.

FINDINGS

81 participants with probable Alzheimer's disease and 69 healthy controls were assessed. Independent visual assessment of the PET scans showed a sensitivity of 80% (95% CI 71-89) and a specificity of 91% (84-98) for discriminating participants with Alzheimer's disease from healthy controls. The SUVRs in all neocortical grey-matter regions in participants with Alzheimer's disease were significantly higher (p < 0·0001) compared with the healthy controls, with the posterior cingulate being the best discriminator. Linear discriminant analysis of regional SUVRs yielded a sensitivity of 85% and a specificity of 91%. Regional SUVRs also correlated well with scores of cognitive impairment such as the MMSE and the word-list memory and word-list recall scores (r -0·27 to -0·33, p ≤ 0·021). APOE ɛ4 was more common in participants with positive PET images compared with those with negative scans (65%vs 22% [p=0·027] in patients with Alzheimer's disease; 50%vs 16% [p = 0·074] in healthy controls). No safety concerns were noted.

INTERPRETATION

We provide verification of the efficacy, safety, and biological relevance of florbetaben (¹⁸F) amyloid-β PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia.

FUNDING

Bayer Schering Pharma AG.

摘要

背景

使用淀粉样蛋白-β PET 成像有可能帮助早期、准确地诊断阿尔茨海默病。氟比洛芬（¹⁸F）是一种有前景的 ¹⁸F 标记的淀粉样蛋白-β靶向 PET 示踪剂，正在临床开发中。我们旨在评估氟比洛芬（¹⁸F）PET 在区分可能患有阿尔茨海默病的患者和老年健康对照者方面的敏感性和特异性。

方法

我们在澳大利亚、德国、瑞士和美国的 18 个中心进行了一项多中心、开放标签、非随机的 2 期研究。对可能患有阿尔茨海默病的患者（年龄 55 岁或以上，迷你精神状态检查[MMSE]评分为 18-26，临床痴呆评定[CDR]为 0.5-2.0）和年龄匹配的健康对照者（MMSE≥28，CDR=0）进行氟比洛芬（¹⁸F）PET 成像。我们的主要目的是根据注射后 90-110 分钟的新皮质示踪剂摄取模式，确定扫描在区分可能患有疾病的患者和年龄匹配的健康对照者方面的诊断效果。PET 图像由三位读者进行视觉评估，这些读者对临床诊断和所有其他临床发现均不知情，并使用预先确定的脑感兴趣区域进行定量评估，以获得标准摄取值比（SUV），将小脑皮质作为参考区域。本研究在 ClinicalTrials.gov 注册，编号为 NCT00750282。

结果

对 81 名可能患有阿尔茨海默病的患者和 69 名健康对照者进行了评估。对 PET 扫描的独立视觉评估显示，对于区分阿尔茨海默病患者和健康对照者，其敏感性为 80%（95%CI 71-89），特异性为 91%（84-98）。与健康对照组相比，阿尔茨海默病患者的所有新皮质灰质区域的 SUV 均显著升高（p<0.0001），其中后扣带回是最佳的鉴别区域。对区域 SUV 的线性判别分析产生了 85%的敏感性和 91%的特异性。区域 SUV 也与认知障碍评分（如 MMSE 和词汇记忆和词汇回忆评分）很好地相关（r=-0.27 至-0.33，p≤0.021）。与阴性扫描相比，APOE ε4 在阳性 PET 图像的患者中更为常见（阿尔茨海默病患者中为 65%比 22%[p=0.027]；健康对照者中为 50%比 16%[p=0.074]）。未发现安全问题。