PET and SPECT Radiotracers for Alzheimer's Disease
2015
The two main pathological hallmarks of Alzheimer’s disease (AD)
in the brain are senile plaques (SPs) composed of beta-amyloid (Aβ) peptides
and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein. These hallmarks are associated with a
cholinergic deficit. While the process leading to the development of AD is complex and multifactorial, and
the etiology of AD is not completely known, it is nowadays clear that AD is a multifaceted illness requiring
the combination of synergetic treatment strategies. Because definite diagnosis is achieved by postmortem examination
of the brain, new noninvasive diagnostic imaging modalities for AD are in high demand, both to
detect and monitor the evolution of this sickness, and evaluate the efficacy of treatments. Positron Emission
Tomography (PET) is a nuclear molecular imaging technique that uses radiopharmaceuticals labeled with a
positron-emitting isotope (carbon-11, fluorine-18, copper-64, gallium- 68…), to visualize in vivo cellular metabolism
with high-spatial resolution and unique sensitivity, while Single-Photon Emission Computed Tomography
(SPECT) using radioisotopes such as technetium-99m or iodine-123. Besides being a powerful tool for
diagnosis (mostly in oncology with [ 18 F]-FDG), PET experiments can provide information about biochemical
mechanisms in living tissues or interactions between neurotransmitter and brain receptors. For the past two
decades, numerous radiopharmaceuticals have been developed for imaging the lesions observed in AD patients.
Tau aggregates and Aβ plaques can also be visualized and quantified by mean of specific radioligands.
The latter has been the focus of intense research efforts lately, leading to new FDA approved radiopharmaceuticals.
This paper aimed at summarizing the recent advances in PET and SPECT imaging of AD pathophysiology.
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