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A hallmark pathology of Alzheimer disease (AD) is the amyloid-beta (Aβ) plaque, which could not be detected during life until recently. Advances have permitted its detection in cerebrospinal fluid and with positron emission tomography (PET) scanning using the [11C]Pittsburgh compound B. However, this compound's short half-life requires local cyclotron production, so it is not clinically useful. Several companies are developing PET amyloid imaging agents labeled with [18F] that could be transported long distances to hospitals and clinics.
For this partially manufacturer-funded study, investigators recruited patients with terminal diseases. Patients were scanned using the PET amyloid imaging agent [18F]florbetapir within 1 year of death; 74 younger, healthy controls were also scanned. Blinded investigators evaluated the images both quantitatively and with visual ratings. Autopsies, performed on 35 of the case patients, included both Aβ measurement with quantitative immunohistochemistry and rating of tissue slides for neuritic plaques.
Regardless of the method used for analysis of the PET and postmortem data, PET image findings obtained during life correlated strongly with the degree of pathology seen at autopsy.
Clark CM et al. Use of florbetapir-PET for imaging β-amyloid pathology. JAMA 2011 Jan 19; 305:275.
Comment
These findings put PET amyloid imaging on a strong footing as a diagnostic tool for AD by showing that it can detect the “gold standard” of pathology required for diagnosis. The participants in this study tended to fall into strongly positive or strongly negative zones; it is unclear whether results might be less accurate in patients with intermediate amounts of Aβ, who would be more typical of individuals seen in clinical practice. Recently, the FDA reviewed the application for approval of this PET radiopharmaceutical, and it seems likely to be approved if clinician interpretation of the images can be shown to be reliable. This imaging modality will provide clinicians with a means of identifying Aβ in living patients. In combination with a careful clinical evaluation, this tool could prove useful in many cases when making the diagnosis is difficult.