Radioligand development for PET imaging of β-amyloid (AD)-current status

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 beta amyloid (A beta) plaque formation. Since neuroprotective treatments are typically most effective at early stages of injury, the detection and measurement of AD load in living brain should be performed at early and perhaps even presymptornatic 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 A beta aggregates. General structure-activity relationships have emerged, including the identification of at least three different ligand binding sites in various A beta aggregates and recognition of the general structural requirements for ligand binding at each site. Also a few radioligands applicable to imaging A beta plaques in living human brain with positron emission tomography (PET) have emerged, including [C-11]PIB, [C-11]SB-13 and [F-18]FDDNP.