Abstract
Multifunctional imaging of the deposition of amyloid-beta (Aβ) aggregates in the brain is of great importance in diagnosing Alzheimer’s disease. Herein, we report a multifunctional Aβ-targeting small-molecular-weight gadolinium (Gd)-based contrast agent (CA), Gd-DO3A-Chal (a new Gd-chelate conjugated with chalcone), that showed 8 times higher binding affinity to Aβ aggregates than a previously reported Gd-chelate conjugated with Pittsburgh compound B. Gd-DO3A-Chal showed multimodal imaging capability. As a new fluorescence imaging probe, Gd-DO3A-Chal showed a good match with immunostained images using 6E10 monoclonal antibodies for the detection of Aβ aggregates in 5XFAD transgenic mouse brain sections. For in vivo magnetic resonance (MR) imaging without blood-brain barrier disruption, longitudinal relaxation time (T1)-weighted MR images after intravenous administration of Gd-DO3A-Chal showed signal enhancement of the Aβ distribution in living 5XFAD transgenic mouse brain. Therefore, in vivo MR images for Aβ detection in addition to fluorescent optical images of Aβ aggregates with high specificity and sensitivity using this new multifunctional Aβ-targeting CA were successfully demonstrated.
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