Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: phase 3 study.

Abstract

BACKGROUND:

Evaluation of brain β-amyloid by positron emission tomography (PET) imaging can assist in the diagnosis of Alzheimer disease (AD) and other dementias.

METHODS:

Open-label, nonrandomized, multicenter, phase 3 study to validate the (18)F-labeled β-amyloid tracer florbetaben by comparing in vivo PET imaging with post-mortem histopathology.

RESULTS:

Brain images and tissue from 74 deceased subjects (of 216 trial participants) were analyzed. Forty-six of 47 neuritic β-amyloid-positive cases were read as PET positive, and 24 of 27 neuritic β-amyloid plaque-negative cases were read as PET negative (sensitivity 97.9% [95% confidence interval or CI 93.8-100%], specificity 88.9% [95% CI 77.0-100%]). In a subgroup, a regional tissue-scan matched analysis was performed. In areas known to strongly accumulate β-amyloid plaques, sensitivity and specificity were 82% to 90%, and 86% to 95%, respectively.

CONCLUSIONS:

Florbetaben PET shows high sensitivity and specificity for the detection of histopathology-confirmed neuritic β-amyloid plaques and may thus be a valuable adjunct to clinical diagnosis, particularly for the exclusion of AD.

TRIAL REGISTRATION:

ClinicalTrials.govNCT01020838.

• Authors: Osama Sabri, Marwan N Sabbagh, John Seibyl, Henryk Barthel, Hiroyasu Akatsu, Yasuomi Ouchi, Kohei Senda, Shigeo Murayama, Kenji Ishii, Masaki Takao, Thomas G Beach, Christopher C Rowe, James B Leverenz, Bernardino Ghetti, James W Ironside, Ana M Catafau, Andrew W Stephens, Andre Mueller, Norman Koglin, Anja Hoffmann, Katrin Roth, Cornelia Reininger, Walter J Schulz-Schaeffer, Florbetaben Phase 3 Study Group
• Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association (Alzheimers Dement) Vol. 11 Issue 8 Pg. 964-74 (Aug 2015) ISSN: 1552-5279 [Electronic] United States
• PMID: 25824567 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Aniline Compounds
• Stilbenes
• 4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (diagnostic imaging, metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Analysis of Variance
• Aniline Compounds (pharmacokinetics)
• Brain (diagnostic imaging, metabolism, pathology)
• Cohort Studies
• Diagnosis
• Female
• Humans
• Image Processing, Computer-Assisted
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Plaque, Amyloid (pathology)
• Positron-Emission Tomography
• Psychiatric Status Rating Scales
• ROC Curve
• Radiography
• Stilbenes (pharmacokinetics)