Alzheimer's Disease: SPECT and PET Tracers for Beta-Amyloid Imaging

Abstract

The definite diagnosis of Alzheimer's disease (AD) is based on the detection of beta amyloid (A beta) plaques and neurofibrillary tangles (NFTs) - which are the pathological hallmarks of the disease- in the postmortem brains. Although regional Cerebral Blood Flow (rCBF) and Cerebral Glucose Metabolism (CGM) abnormalities have already been studied in AD patients with Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET), the development of specific imaging agents for direct mapping of A beta plaques in the living brain, is a great challenge. A beta probes could significantly contribute to the early diagnosis of AD, the elucidation of the underlying neuropathological processes and the evaluation of anti-amyloid therapies which are currently under investigation. The development of SPECT and PET tracers for A beta imaging represents an active area in radiopharmaceutical design. A beta substantial number of potential A beta imaging radioligands have been designed and used in-vitro. They are either monoclonal antibodies to A beta and radiolabeled A beta peptides, or derivatives of histopathological stains such as Congo red (CR), chrysamine-G (CG) and Thioflavin T (TT). Though, only few of them, that display high binding affinity to A beta as well as sufficient brain penetration, have been used primarily in in-vivo studies and to a smaller degree on human subjects. Since A beta plaques are not homogenous and contain multiple binding sites that can accommodate structurally diverse compounds, they offer flexibility in designing various different probes, as potential amyloid imaging agents.