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Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status

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Two of the main pathological hallmarks of Alzheimer's disease (AD) are neuritic plaques and neurofibrillary tangles. Significant evidence supports a critical and probable causative role of βamyloid (Aβ) plaque formation. Since neuroprotective treatments are typically most effective at early stages of injury, the detection and measurement of Aβ load in living brain should be performed at early and perhaps even presymptomatic stages of AD. Two primary targets of molecular imaging research with positron emission tomography (PET) are to develop surrogate markers (radioligands) for assessing disease progression and for monitoring the efficacy of developmental therapeutics. Here, we review the current status of radioligand development for PET imaging of Aβ aggregates. General structure-activity relationships have emerged, including the identification of at least three different ligand binding sites in various Aβ aggregates and recognition of the general structural requirements for ligand binding at each site. Also a few radioligands applicable to imaging Aβ plaques in living human brain with positron emission tomography (PET) have emerged, including [11C]PIB, [11C]SB- 13 and [18F]FDDNP.

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Keywords: Alzheimer's disease; PET imaging; assay; radioligand; β-amyloid

Document Type: Research Article

Affiliations: Molecular Imaging Branch,National Institute of Mental Health, National Institutes of Health, Bethesda,MD 20892, USA.

Publication date: 01 January 2007

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