title: Diagnostic accuracy of (18)F amyloid PET tracers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Morris
authors.affiliation: King's Technology Evaluation Centre, King's College London, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK. anastasia.chalkidou@kcl.ac.uk.|Department of Biomedical Engineering, Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London, UK. anastasia.chalkidou@kcl.ac.uk.
authors.forename: Anastasia
authors.identifier: http://orcid.org/0000-0002-7519-8774
authors.initials: A
authors.lastname: Chalkidou
authors.affiliation: Department of Biomedical Engineering, Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hammers
authors.affiliation: King's Technology Evaluation Centre, King's College London, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK.|Division of Health and Social Care Research, King's College London, London, UK.|NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Peacock
authors.affiliation: King's Technology Evaluation Centre, King's College London, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK.|Division of Health and Social Care Research, King's College London, London, UK.|NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, King's College London, London, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Summers
authors.affiliation: 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.|Department of Medical Physics, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Keevil
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D000814:Aniline Compounds / Q000009:adverse effects*; D052160:Benzothiazoles / Q000009:adverse effects*; D016022:Case-Control Studies; D005026:Ethylene Glycols / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods / Q000592:standards*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013267:Stilbenes / Q000009:adverse effects*
chemical_list: D000814:Aniline Compounds; D052160:Benzothiazoles; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; D013267:Stilbenes; C581552:flutemetamol; C545186:florbetapir; C527756:4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene
keywords: Alzheimer’s disease; Amyloid; Florbetaben; Florbetapir; Flutemetamol; PET