Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism.

Abstract

BACKGROUND:

Amyloid-beta (Abeta) plaque formation is a hallmark of Alzheimer's disease (AD) and precedes the onset of dementia. Abeta imaging should allow earlier diagnosis, but clinical application is hindered by the short decay half-life of current Abeta-specific ligands. (18)F-BAY94-9172 is an Abeta ligand that, due to the half-life of (18)F, is suitable for clinical use. We thus studied the effectiveness of this ligand in identifying patients with AD.

METHODS:

15 patients with mild AD, 15 healthy elderly controls, and five individuals with frontotemporal lobar degeneration (FTLD) were studied. (18)F-BAY94-9172 binding was quantified by use of the standardised uptake value ratio (SUVR), which was calculated for the neocortex by use of the cerebellum as reference region. SUVR images were visually rated as normal or AD.

FINDINGS:

(18)F-BAY94-9172 binding matched the reported post-mortem distribution of Abeta plaques. All AD patients showed widespread neocortical binding, which was greater in the precuneus/posterior cingulate and frontal cortex than in the lateral temporal and parietal cortex. There was relative sparing of sensorimotor, occipital, and medial temporal cortex. Healthy controls and FTLD patients showed only white-matter binding, although three controls and one FTLD patient had mild uptake in frontal and precuneus cortex. At 90-120 min after injection, higher neocortical SUVR was observed in AD patients (2.0 [SD 0.3]) than in healthy controls (1.3 [SD 0.2]; p<0.0001) or FTLD patients (1.2 [SD 0.2]; p=0.009). Visual interpretation was 100% sensitive and 90% specific for detection of AD.

INTERPRETATION:

(18)F-BAY94-9172 PET discriminates between AD and FTLD or healthy controls and might facilitate integration of Abeta imaging into clinical practice.

• Authors: Christopher C Rowe, Uwe Ackerman, William Browne, Rachel Mulligan, Kerryn L Pike, Graeme O'Keefe, Henry Tochon-Danguy, Gordon Chan, Salvatore U Berlangieri, Gareth Jones, Kerryn L Dickinson-Rowe, Hank P Kung, Wei Zhang, Mei Ping Kung, Daniel Skovronsky, Thomas Dyrks, Gerhard Holl, Sabine Krause, Matthias Friebe, Lutz Lehman, Stefanie Lindemann, Ludger M Dinkelborg, Colin L Masters, Victor L Villemagne
• Journal: The Lancet. Neurology (Lancet Neurol) Vol. 7 Issue 2 Pg. 129-35 (Feb 2008) ISSN: 1474-4422 [Print] England
• PMID: 18191617 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (diagnosis, diagnostic imaging, metabolism)
• Amyloid beta-Peptides (metabolism)
• Aniline Compounds (chemical synthesis)
• Brain (diagnostic imaging)
• Dementia (diagnosis, diagnostic imaging)
• Diagnosis, Differential
• Female
• Humans
• Image Interpretation, Computer-Assisted
• Isotope Labeling
• Male
• Middle Aged
• Plaque, Amyloid (diagnostic imaging, metabolism)
• Positron-Emission Tomography
• Radiopharmaceuticals (chemical synthesis)
• Stilbenes (chemical synthesis)