Fluorine-18 radiolabeled heterocycles as PET tracers for imaging β-amyloid plaques in Alzheimer's disease.

Alzheimer's disease (AD), the most common form of dementia, is a progressive and fatal neurodegenerative disorder. The neuropathological hallmarks of AD generally revealed on postmortem brain tissue are the extracellular neuritic plaque deposits and intracellular neurofibrillary tangles. Significant evidence supports the pivotal role of β-amyloid peptides in the pathogenesis of AD. Therefore, The ability to image β-amyloid plaques in brain with noninvasive techniques such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) may not only aid in presymptomatic identification of AD patients and differential diagnosis of patients with dementia, but also monitoring the effectiveness of anti-amyloid therapeutic strategies. For these reasons, development of β-amyloid plaque-specific imaging agents has been extensively pursued and reported. This review summarizes the current status of (18)F-labeled radioligand development for PET imaging of β-amyloid plaques. [(18)F]FDDNP is the first PET radioligand that demonstrated differential uptake and retention in the brain of AD patients, while a low signal-to-noise ratio in PET studies was indicated. At this time, [(18)F]3'-F-PIB (flutemetamol), [(18)F]AV-1 (florbetaben), [(18)F]AZD4694, and [(18)F]MK-3328 are undergoing phase II and III clinical trial. [(18)F]AV-45 (florbetapir) has recently been approved by FDA for use in patients being evaluated for Alzheimer's disease and other causes of cognitive decline. Several other (18)F-labeled radioligands based upon imidazo[1,2-a]pyridine, benzothiazole, stilbene, benzofuran, and benzoxazole core structures have also been synthesized and evaluated.