Amyloid β-binding Bifunctional Chelators with Favorable Lipophilicity for 64Cu PET Imaging in Alzheimer’s Disease
semanticscholar(2021)
摘要
Herein we report a
new series of bifunctional chelators (BFCs) with high affinity for amyloid
aggregates, strong binding affinity towards Cu(II) and favorable lipophilicity
for potential blood-brain barrier (BBB) penetration. The alkyl carboxylate
pendant arms offer up to three orders of magnitude higher binding affinity
towards Cu(II) vs. the parent chelating fragment, and can generate fairly
stable Cu complexes, including 64Cu-radiolabeled compounds. Among
the five compounds tested, the 64Cu-YW-7 and 64Cu-YW-10
complexes exhibit strong and specific staining of amyloid plaques in ex vivo
autoradiography studies. Importantly, these compounds have promising partition
coefficient (Log D) values of 0.91-1.26 and show moderate brain uptake in
biodistribution studies using CD-1 mice. Overall, these BFCs could serve as
lead compounds for the development of positron emission tomography (PET)
imaging agents for AD diagnosis.
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