Despite the wide use of magnetic resonance imaging (MRI) as a clinical diagnostic tool, there are still no clinically approved MRI contrast agents that can be applied for cerebral Alzheimer’s disease (AD) biomarker imaging. We report here the design and development of the first amyloid-β (Aβ)-targeted, blood–brain barrier (BBB) penetrable theranostic Gd(DOTA)-cyanine dyad, which was synthesized by the conjugation of Gd(DOTA) complex and carbazole-based cyanine dye by the copper(I)-catalyzed azide-alkyne cycloaddition click reaction for imaging of Aβ in vivo and ex vivo in AD mouse models. This dyad, as a multimodal probe, possesses desirable multifunctional properties, including good biocompatibility, low cytotoxicity, high Aβ selectivity, strong fluorescence enhancement upon binding with Aβ species, good paramagnetic properties, high stability, good BBB penetrability, and fast elimination from the mouse. The longitudinal relaxivity (r1) of the dyad was found to be 4.42 mM–1 s–1 at 3 T, suggesting it to be promising as a T1-weighted MRI contrast agent. The probe has been successfully demonstrated to be able to be applied for one- and two-photon excited fluorescence and magnetic resonance (MR) imaging of Aβ in transgenic mouse models of AD. In addition, it can inhibit Aβ aggregation, protect against toxicity induced by Aβ, and suppress Aβ-induced reactive oxygen species (ROS) production. Our results demonstrate the highly promising theranostic capability of the dyad for diagnosis and therapy of AD and extraordinary potential for MRI of Aβ in humans.
- amyloid-β targeting
- gadolinium(III) complex-cyanine
- in vivo MR imaging
- multimodal contrast agent