Morris Elizabeth, Chalkidou Anastasia, Hammers Alexander, Peacock Janet, Summers Jennifer, Keevil Stephen
King's Technology Evaluation Centre, King's College London, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK.
Department of Biomedical Engineering, Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London, UK.
Eur J Nucl Med Mol Imaging. 2016 Feb;43(2):374-385. doi: 10.1007/s00259-015-3228-x. Epub 2015 Nov 28.
Imaging or tissue biomarker evidence has been introduced into the core diagnostic pathway for Alzheimer's disease (AD). PET using (18)F-labelled beta-amyloid PET tracers has shown promise for the early diagnosis of AD. However, most studies included only small numbers of participants and no consensus has been reached as to which radiotracer has the highest diagnostic accuracy. First, we performed a systematic review of the literature published between 1990 and 2014 for studies exploring the diagnostic accuracy of florbetaben, florbetapir and flutemetamol in AD. The included studies were analysed using the QUADAS assessment of methodological quality. A meta-analysis of the sensitivity and specificity reported within each study was performed. Pooled values were calculated for each radiotracer and for visual or quantitative analysis by population included. The systematic review identified nine studies eligible for inclusion. There were limited variations in the methods between studies reporting the same radiotracer. The meta-analysis results showed that pooled sensitivity and specificity values were in general high for all tracers. This was confirmed by calculating likelihood ratios. A patient with a positive ratio is much more likely to have AD than a patient with a negative ratio, and vice versa. However, specificity was higher when only patients with AD were compared with healthy controls. This systematic review and meta-analysis found no marked differences in the diagnostic accuracy of the three beta-amyloid radiotracers. All tracers perform better when used to discriminate between patients with AD and healthy controls. The sensitivity and specificity for quantitative and visual analysis are comparable to those of other imaging or biomarker techniques used to diagnose AD. Further research is required to identify the combination of tests that provides the highest sensitivity and specificity, and to identify the most suitable position for the tracer in the clinical pathway.
影像学或组织生物标志物证据已被纳入阿尔茨海默病（AD）的核心诊断流程。使用（18）F标记的β-淀粉样蛋白PET示踪剂进行的PET检查已显示出对AD早期诊断的前景。然而，大多数研究仅纳入了少量参与者，对于哪种放射性示踪剂具有最高的诊断准确性尚未达成共识。首先，我们对1990年至2014年间发表的文献进行了系统综述，以探索氟贝他班、氟代硼吡咯和氟替美莫在AD诊断中的准确性。采用QUADAS方法学质量评估对纳入的研究进行分析。对每项研究报告的敏感性和特异性进行荟萃分析。计算每种放射性示踪剂以及按人群进行视觉或定量分析的合并值。系统综述确定了9项符合纳入标准的研究。报告相同放射性示踪剂的研究之间方法差异有限。荟萃分析结果表明，所有示踪剂的合并敏感性和特异性值总体较高。通过计算似然比得到了证实。阳性比值的患者比阴性比值的患者患AD的可能性要大得多，反之亦然。然而，仅将AD患者与健康对照进行比较时，特异性更高。这项系统综述和荟萃分析发现，三种β-淀粉样蛋白放射性示踪剂在诊断准确性方面没有显著差异。所有示踪剂在用于区分AD患者和健康对照时表现更好。定量和视觉分析的敏感性和特异性与用于诊断AD的其他影像学或生物标志物技术相当。需要进一步研究以确定提供最高敏感性和特异性的检测组合，并确定示踪剂在临床流程中最合适的位置。
