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
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Journal ArticleDOI
Quantification of 18F-florbetapir PET: comparison of two analysis methods
Chloe Hutton,Jerome Declerck,Mark A. Mintun,Michael Pontecorvo,Michael D. Devous,Abhinay Joshi +5 more
TL;DR: Automatic florbetapir PET quantification using sPAP yielded cortex to cerebellum SUVRs which were correlated and in good agreement with the well-established research method.
Journal ArticleDOI
Interaction of PiB-derivative metal complexes with beta-amyloid peptides: selective recognition of the aggregated forms.
André F. Martins,David M. Dias,Jean-François Morfin,Sara Lacerda,Douglas V. Laurents,Éva Tóth,Carlos F. G. C. Geraldes +6 more
TL;DR: Time-dependent circular dichroism, dynamic light scattering, and TEM investigations of the secondary structure and of the aggregation of Aβ1-40 in the presence of increasing amounts of the metal complexes provide coherent data showing that, despite their structural similarity, the two complexes affect Aβ fibril formation distinctly.
Journal ArticleDOI
Perspectives for multimodal neurochemical and imaging biomarkers in Alzheimer's disease.
Stefan J. Teipel,Stefan J. Teipel,Osama Sabri,Michel J. Grothe,Henryk Barthel,David Prvulovic,Katharina Buerger,Arun L.W. Bokde,Michael Ewers,Wolfgang Hoffmann,Wolfgang Hoffmann,Harald Hampel +11 more
TL;DR: In vivo markers of key events in AD pathogenesis integrated into a heuristic framework that makes strong predictions on pattern of multimodal biomarkers in different stages of AD are available for the first time.
Journal ArticleDOI
Post-mortem analyses of PiB and flutemetamol in diffuse and cored amyloid-β plaques in Alzheimer's disease.
Milos D. Ikonomovic,Christopher Buckley,Eric E. Abrahamson,Julia Kofler,Chester A. Mathis,William E. Klunk,Gill Farrar +6 more
TL;DR: Results indicate that [18F]flutemetamol and [11C]PiB PET signal is influenced by both diffuse plaques and cored plaques, and therefore is likely a function of plaque size and density of Aβ fibrils in plaques.
Critical review of the Appropriate Use Criteria for amyloid imaging: Effect on diagnosis and patient care
Liana G. Apostolova,Janelle M. Haider,Naira Goukasian,Gil D. Rabinovici,Gaël Chételat,John M. Ringman,Sarah Kremen,Joshua D. Grill,Lucas Restrepo,Mario F. Mendez,Daniel H.S. Silverman +10 more
TL;DR: The utility of the Appropriate Use Criteria (AUC) for amyloid imaging is not established.
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