Fluorine-18 Radiolabeled Heterocycles as PET Tracers for Imaging β - Amyloid Plaques in Alzheimer’s Disease
Mark M. Goodman.
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 plaquespecific
imaging agents has been extensively pursued and reported. This review summarizes the current status of 18Flabeled
radioligand development for PET imaging of β-amyloid plaques. [18F]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, [18F]3’-F-PIB (flutemetamol), [18F]AV-1 (florbetaben), [18F]AZD4694, and [18F]MK-3328 are
undergoing phase II and III clinical trial. [18F]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 18F-labeled radioligands
based upon imidazo[1,2-a]pyridine, benzothiazole, stilbene, benzofuran, and benzoxazole core structures have also been
synthesized and evaluated.
Keywords: Alzheimer’s disease, β-amyloid plaques, fluorine-18, heterocycles, PET imaging, radioligands.
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