Journal ArticleDOI
Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study
Henryk Barthel,Hermann-Josef Gertz,Stefan Dresel,Oliver Peters,Peter Bartenstein,Katharina Buerger,Florian Hiemeyer,Sabine M Wittemer-Rump,John Seibyl,Cornelia Reininger,Osama Sabri +10 more
TLDR
The diagnostic efficacy of the scans was established 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 and the sensitivity and specificity of florbetaben (¹⁸F) PET was assessed.Abstract:
Summary Background Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer's disease. Florbetaben ( 18 F) is a promising 18 F-labelled amyloid-β-targeted PET tracer in clinical development. We aimed to assess the sensitivity and specificity of florbetaben ( 18 F) 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 ( 18 F) 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 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 ( 18 F) amyloid-β PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia. Funding Bayer Schering Pharma AG.read more
Citations
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Journal ArticleDOI
Mild to moderate Alzheimer dementia with insufficient neuropathological changes.
Alberto Serrano-Pozo,Jing Qian,Sarah E. Monsell,Deborah Blacker,Teresa Gomez-Isla,Rebecca A. Betensky,John H. Growdon,Keith A. Johnson,Matthew P. Frosch,Reisa A. Sperling,Bradley T. Hyman +10 more
TL;DR: The 2005–2013 National Alzheimer's Coordinating Center autopsy database is examined and it is found that ∼14% of autopsied subjects clinically diagnosed with mild‐to‐moderate probable AD have no or sparse neuritic plaques, which would expectedly yield a negative amyloid PET scan.
Journal ArticleDOI
SPECT and PET imaging in Alzheimer’s disease
Varvara Valotassiou,Julia Malamitsi,John Papatriantafyllou,Efthimios Dardiotis,Ioannis Tsougos,Dimitrios Psimadas,Sotiria Alexiou,George Hadjigeorgiou,George Hadjigeorgiou,Panagiotis Georgoulias +9 more
TL;DR: SPECT and PET have proposed to serve as biomarkers in recently revised diagnostic clinical criteria for the early diagnosis of AD and the prediction of progression to AD in mild cognitive impairment (MCI) subjects.
Journal ArticleDOI
Evaluation of early-phase [18F]-florbetaben PET acquisition in clinical routine cases.
Sonja Daerr,Matthias Brendel,Christian Zach,Erik Mille,Dorothee Schilling,Mathias J. Zacherl,Katharina Bürger,Adrian Danek,Oliver Pogarell,Andreas Schildan,Marianne Patt,Henryk Barthel,Osama Sabri,Peter Bartenstein,Axel Rominger +14 more
TL;DR: Early-phase FBB acquisitions correlate on a relative quantitative and visual level with FDG PET scans, irrespective of the amyloid plaque density assessed in late FBB imaging, suggesting it as a valid surrogate marker for synaptic dysfunction, which could ultimately circumvent the need for additionalFDG PET investigation in diagnosis of dementia.
Book ChapterDOI
Using Pittsburgh Compound B for in vivo PET imaging of fibrillar amyloid-beta.
Ann D. Cohen,Gil D. Rabinovici,Chester A. Mathis,William J. Jagust,William E. Klunk,Milos D. Ikonomovic +5 more
TL;DR: The application of one of the most broadly studied and widely used Aβ imaging agents, Pittsburgh Compound-B (PiB), is discussed.
Journal ArticleDOI
Optimized classification of 18 F-Florbetaben PET scans as positive and negative using an SUVR quantitative approach and comparison to visual assessment.
Santiago Bullich,John Seibyl,Ana M. Catafau,Aleksandar Jovalekic,Norman Koglin,Henryk Barthel,Osama Sabri,Susan De Santi +7 more
TL;DR: The accurate scan classification obtained in this study supports the use of VA as SoT to generate site-specific SUVR cutoffs and emphasizes the additional contribution that SUVR cutoff classification may have compared with VA performed by non-expert readers.
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