Abstract
The presence of ß-amyloid plaques in the brain is a hallmark of Alzheimer's disease (AD) and serves as biomarker for confirmation of diagnosis postmortem. Several positron emission tomography (PET) radioligands that bind selectively to ß-amyloid are currently under clinical development for in vivo imaging of brain amyloid. [18F]AV45 (florbetapir F 18) and [18F]Bay94-9172 (florbetaben) are stilbene derivatives, where as [18F]GE067 (F-PIB, flutemetamol) and [18F]AZD4694 have been derived from Thioflavin t. Few studies have evaluated the mutual binding interaction between these two classes of PET amyloid imaging agents in a head-to-head comparison. β-Amyloid binding capability and cross competition will be evaluated by [3H]AZD4694 and [3H]AV45 binding to synthetic β-amyloid fibrils as well cortical sections from human AD brain. Selectivity of binding to β-amyloid plaques and degree of nonspecific interactions will further be explored using autoradiography in cortical sections from human AD brain as well tg2576 mice. In the present study we will evaluated and compare imaging properties emphasizing on affinity and degree of nonspecific interaction of AZD4694 and AV45 in vitro. Accumulated results show that build up of brain β-amyloid deposits is a very early event in preclinical AD. The ability to successfully determine early changes in β-amyloid build up in the living brain will require PET radioligands with high affinity and low degree of homogenous nonspecific interaction.
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