Ga-68-Bivalent Polypegylated Styrylpyridine Conjugates For Imaging A Beta Plaques In Cerebral Amyloid Angiopathy
BIOCONJUGATE CHEMISTRY(2016)
摘要
A beta plaques deposited on blood vessels are associated with cerebral amyloid angiopathy (CAA). In an effort to selectively map these A beta plaques, we are reporting a new series of Ga-68 labeled styrylpyridine derivatives with high molecular weights. In vitro binding to A beta plaques in postmortem Alzheimer's disease (AD) brain tissue showed that these Ga-68 labeled bivalent styrylpyridines displayed good affinities and specificity (K-i < 30 nM). In vitro autoradiography using post-mortem AD brain sections showed specific binding of these Ga-68 complexes to A beta plaques. Biodistribution studies in normal mice showed very low initial brain uptakes (<0.3% dose/g) indicating a low blood-brain barrier (BBB) penetration. The preliminary results suggest that Ga-68 labeled bivalent styrylpyridines may be promising candidates as PET imaging radiotracers for detecting CAA.
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