Multifunctional imaging of amyloid-beta peptides with a new gadolinium-based contrast agent in Alzheimer's disease

Abstract

Multifunctional imaging of the deposition of amyloid-beta (A beta) aggregates in the brain is of great importance in diagnosing Alzheimer's disease. Herein, we report a multifunctional A beta-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 A beta aggregates than a previously reported Gd-chelate conjugated with Pittsburgh compound B. Gd-DO3A-Chat 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 A beta aggregates in 5XFAD transgenic mouse brain sections. For in vivo magnetic resonance (MR) imaging without blood-brain barrier disruption, longitudinal relaxation time (T-1)-weighted MR images after intravenous administration of Gd-DO3A-Chal showed signal enhancement of the A beta distribution in living 5XFAD transgenic mouse brain. Therefore, in vivo MR images for A beta detection in addition to fluorescent optical images of A beta aggregates with high specificity and sensitivity using this new multifunctional A beta-targeting CA were successfully demonstrated. (C) 2019 Published by Elsevier B.V. on behalf of The Korean Society of Industrial and Engineering Chemistry.