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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Longitudinal Assessment of Cerebral β-Amyloid Deposition in Mice Overexpressing Swedish Mutant β-Amyloid Precursor Protein Using 18F-Florbetaben PET
Axel Rominger,Matthias Brendel,Steffen Burgold,Kevin Keppler,Karlheinz Baumann,Guoming Xiong,Erik Mille,Franz-Josef Gildehaus,Janette Carlsen,Juli Schlichtiger,Sabrina Niedermoser,Björn Wängler,Paul Cumming,Harald Steiner,Harald Steiner,Jochen Herms,Christian Haass,Christian Haass,Peter Bartenstein +18 more
TL;DR: In the first longitudinal PET study in an AD mouse model using the novel β-amyloid tracer 18F-florbetaben, the temporal and spatial progression of amyloidogenesis in the brain of APP-Swe mice were sensitively monitored and should afford the means for preclinical testing of novel therapeutic approaches to the treatment of AD.
Journal ArticleDOI
A systematic review and meta-analysis of 18F-labeled amyloid imaging in Alzheimer's disease
TL;DR: Amyloid imaging using fluorine 18–labeled tracers florbetapir, flor betaben, and flutemetamol has recently been reported in Alzheimer's disease (AD).
Journal ArticleDOI
Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease
Raymond Scott Turner,Michaeline Hebron,Abigail Lawler,Elizabeth E. Mundel,Nadia Yusuf,J. Nathan Starr,Muhammad Anjum,Fernando Pagan,Yasar Torres-Yaghi,Wangke Shi,Sanjana Mulki,Dalila Ferrante,Sara Matar,Xiaoguang Liu,Giuseppe Esposito,Frank Berkowitz,Xiong Jiang,Jaeil Ahn,Charbel Moussa +18 more
TL;DR: Preclinical evidence with nilotinib, a US Food and Drug Administration‐approved drug for leukemia, indicates improvement in Alzheimer's disease phenotypes and alters biomarkers and clinical decline in Alzheimer’s disease.
Journal ArticleDOI
Age dependence of brain β-amyloid deposition in Down syndrome An [18F]florbetaben PET study
Danna Jennings,John Seibyl,Marwan N. Sabbagh,Florence Lai,William Hopkins,Santi Bullich,Monica Gimenez,Cornelia Reininger,Barbara Putz,Andrew Stephens,Ana M. Catafau,Ken Marek +11 more
TL;DR: Subjects with DS who have no evidence of dementia demonstrate brain-amyloid binding in vivo, suggesting that [18F]florbetaben PET imaging may detect &bgr;-AMyloid in this at-risk population.
Journal ArticleDOI
Combined PET/MRI: Multi-modality Multi-parametric Imaging Is Here: Summary Report of the 4th International Workshop on PET/MR Imaging; February 23-27, 2015, Tübingen, Germany.
Dale L. Bailey,Dale L. Bailey,Bernd J. Pichler,B. Gückel,Henryk Barthel,A. J. Beer,Jens Bremerich,Johannes Czernin,Alexander Drzezga,Christiane Franzius,Vicky Goh,Vicky Goh,Markus Hartenbach,H. Iida,Andreas Kjaer,C la Fougère,Claes Nøhr Ladefoged,Ian Law,Konstantin Nikolaou,Harald H. Quick,Osama Sabri,Jürgen F. Schäfer,Michael Schäfers,Hans F. Wehrl,Thomas Beyer +24 more
TL;DR: This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET) and MRI systems that was held in Tübingen, Germany, from February 23 to 27, 2015.
References
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Marshal F. Folstein,Marshal F. Folstein,Susan E B Folstein,Susan E B Folstein,Paul R. McHugh,Paul R. McHugh +5 more
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A practical method for grading the cognitive state of patients for the clinician
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Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain
Nathalie Tzourio-Mazoyer,B. Landeau,D. Papathanassiou,Fabrice Crivello,Octave Etard,Nicolas Delcroix,Bernard Mazoyer,Marc Joliot +7 more
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