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RGD-Peptide Functionalization Affects the In Vivo Diffusion of a Responsive Trimeric MRI Contrast Agent through Interactions with Integrins

MPS-Authors
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Gambino,  G
Research Group MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Gambino,  T
Research Group MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Connah,  L
Research Group MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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La Cava,  F
Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Evrard,  H
Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Angelovski,  G
Research Group MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Citation

Gambino, G., Gambino, T., Connah, L., La Cava, F., Evrard, H., & Angelovski, G. (2021). RGD-Peptide Functionalization Affects the In Vivo Diffusion of a Responsive Trimeric MRI Contrast Agent through Interactions with Integrins. Journal of Medicinal Chemistry, Epub ahead. doi:10.1021/acs.jmedchem.1c00264.


Cite as: http://hdl.handle.net/21.11116/0000-0008-7E10-9
Abstract
The relevance of MRI as a diagnostic methodology has been expanding significantly with the development of molecular imaging. Partially, the credit for this advancement is due to the increasing potential and performance of targeted MRI contrast agents, which are able to specifically bind distinct receptors or biomarkers. Consequently, these allow for the identification of tissues undergoing a disease, resulting in the over- or underexpression of the particular molecular targets. Here we report a multimeric molecular probe, which combines the established targeting properties of the Arg-Gly-Asp (RGD) peptide sequence toward the integrins with three calcium-responsive, Gd-based paramagnetic moieties. The bifunctional probe showed excellent 1H MRI contrast enhancement upon Ca2+ coordination and demonstrated a longer retention time in the tissue due to the presence of the RGD moiety. The obtained results testify to the potential of combining bioresponsive contrast agents with targeting vectors to develop novel functional molecular imaging methods.