18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial.

Abstract

OBJECTIVE:

The most widely studied positron emission tomography ligand for in vivo beta-amyloid imaging is (11)C-Pittsburgh compound B ((11)C-PIB). Its availability, however, is limited by the need for an on-site cyclotron. Validation of the (18)F-labeled PIB derivative (18)F-flutemetamol could significantly enhance access to this novel technology.

METHODS:

Twenty-seven patients with early-stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of (18)F-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for (18)F-flutemetamol and its parent molecule (11)C-PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test-retest variability of (18)F-flutemetamol SUVRs in 5 of the AD subjects.

RESULTS:

Blinded visual assessments of (18)F-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical (18)F-flutemetamol SUVRs and (11)C-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%.

INTERPRETATION:

(18)F-Flutemetamol performs similarly to the (11)C-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use.

• Authors: Rik Vandenberghe, Koen Van Laere, Adrian Ivanoiu, Eric Salmon, Christine Bastin, Eric Triau, Steen Hasselbalch, Ian Law, Allan Andersen, Alex Korner, Lennart Minthon, Gaëtan Garraux, Natalie Nelissen, Guy Bormans, Chris Buckley, Rikard Owenius, Lennart Thurfjell, Gill Farrar, David J Brooks
• Journal: Annals of neurology (Ann Neurol) Vol. 68 Issue 3 Pg. 319-29 (Sep 2010) ISSN: 1531-8249 [Electronic] United States
• PMID: 20687209 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
• Aniline Compounds
• Benzothiazoles
• Radiopharmaceuticals
• Thiazoles
• Fluorodeoxyglucose F18

Topics

• Aged
• Alzheimer Disease (diagnostic imaging)
• Aniline Compounds
• Benzothiazoles
• Brain (diagnostic imaging, metabolism)
• Cognition Disorders (diagnostic imaging)
• Diagnostic Imaging
• Fluorodeoxyglucose F18 (analogs & derivatives)
• Humans
• Middle Aged
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals
• Sensitivity and Specificity
• Thiazoles