Development and evaluation of compounds for imaging of β-amyloid plaque by means of positron emission tomography
The proof of concept for in vivo targeting of β-amyloid plaques (Aβ) in patients with Alzheimer’s disease (AD) by means of nuclear imaging methods has been shown in recent clinical studies.
For positron emission tomography (PET), the five compounds [11C]PIB, 3′[18F]FPIB, [18F]FDDNP, [11C]SB-13 and [18F]F-SB-13 have been developed by a formal charge neutralisation of agents used for staining of AD brain post mortem.
In AD-patients, these compounds have been shown to possess a selective uptake in the brain regions known to have a high Aβ-load. Progress towards tracers with proportionality between tracer uptake and quantity of Aβ-load, of use for longitudinal studies of AD patients, is addressed in the current development of Aβ-tracers.
Despite the extensive information on the structure–affinity relationship of several Aβ-binding compounds, data on the regional brain binding kinetics—beyond uptake in healthy rodents—have been obtained only for a few compounds. Recent results indicate that PET-imaging of Aβ-deposits in transgenic rodent models of AD is feasible which may be valuable for a more relevant preclinical evaluation of Aβ-tracers.
KeywordsAlzheimer’s disease Amyloid plaque Nuclear imaging PET SPECT
frontotemporal lobar degeneration
progressive supranuclear palsy
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