159 The poor correlation

between [11C]PIB binding and cognitive impairment has suggested that this imaging test must be interpreted with caution and has raised questions about the role of Aβ protein as a contributor to the overall disease process. Nevertheless, [11C]PIB PET imaging appears to be able to detect prodromal AD Pim inhibitor earlier and to better distinguish between MCI subtypes than [18F]FDG PET160 However, metabolic abnormalities in the brain closely parallel cognitive deficits, and share a more regionally specified distribution compared with β-amyloid deposits. 161 Although PIB has proven very informative for studying AD, the short half-life Inhibitors,research,lifescience,medical of carbon-11 limits its clinical application to centres with an on-site cyclotron. Inhibitors,research,lifescience,medical Consequently considerable effort has gone into developing fluorinated tracers for amyloid plaques and this has resulted in [18F]flutemetamol,

[18F]florbetapir, [18F]florbetaben, and other fluorinated equivalents of [11C]PIB157 being developed. One of these, [18F]florbelapir (AMYViDTM, Eli Lilly), has recently been approved by the FDA for PET imaging of β-amyloid neuritic plaques in the living brain. The sensitivity of [18F]florbetapir scans for the detection of β-amyloid neuritic plaques was 92% (range, 69 to 95) and the specificity was 95% (range, 90 to 100).162 Accurate and reliable Inhibitors,research,lifescience,medical estimation of the density of β amyloid neuritic plaques by [18F]florbetapir was verified through clinical and nonclinical studies and it is expected to provide prognostic and predictive information in AD.162 Molecular imaging has enabled the investigation of other aspects of the pathophysiological process Inhibitors,research,lifescience,medical in AD, such as neuroinflammation. The PET tracer [11C]PK11195 provides a measure of the activation of microglia Inhibitors,research,lifescience,medical in the brain, reflecting neuroinflammation. Studies have found elevated [11C]PK11195 binding in the temporoparietal, cingulate, and entorhinal cortex

in AD,163 which was also correlated with impairments in cognitive performance.164 Activation of astrocytes, as imaged with [11C]DED, has also been shown to be increased in AD and mild cognitive impairment (MCI),165 which is a syndrome defined as cognitive decline greater than expected for an individual’s age and education level that can be a precursor to AD.166 Moreover, MCI demonstrated higher [11C]DED binding than AD suggesting the activation of Olopatadine astrocyte could be an early dynamic phenomenon in the time course of AD.165 As such, each tracer has its advantages and their combined use is expected to detect the earliest AD pathogenic events, improve classification and monitor progression.167 The Alzheimer’s Disease Neuroimaging Initiative (ADNI), a global research effort, has endeavored to validate such biomarkers for the early detection and tracking of AD.