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Bioresponsive MRI Agents: Insights from Coordination Chemistry

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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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Angelovski, G. (2016). Bioresponsive MRI Agents: Insights from Coordination Chemistry. Talk presented at 42nd International Conference on Coordination Chemistry (ICCC 2016). Brest, France. 2016-07-03 - 2016-07-08.


Cite as: http://hdl.handle.net/21.11116/0000-0000-7CA6-A
Abstract
Bioresponsive or smart contrast agents (SCAs) can substantially improve the specificity of magnetic resonance imaging (MRI) in studying processes on molecular and cellular level. These probes can alternate their MR signals upon change in the local environment, thus reporting the occurrence of a particular physiological or pathological process. Monitoring changes in concentration of ions or molecules that are involved in neuronal signaling with SCAs could be extremely valuable for MR neuroimaging and allow investigation of brain activity in unprecedented fashion. To this end, we developed a series of cyclen-based paramagnetic complexes that strongly respond to calcium ions and amino-acid neurotransmitters. They possess a common chelator of the paramagnetic ion covalently linked to EGTA-derived moiety or aza-crown ether to achieve an interaction with calcium ions or neurotransmitters, respectively. 1-2 The high-resolution NMR and DFT studies revealed dramatic calcium-induced changes in the coordination of the paramagnetic ion and its chelator, which result in the altered hydration of the complex and its extraordinary relaxometric response.1 This response remains strong upon various synthetic modifications of these SCAs and can be detected ex vivo and in vivo.2,3 The obtained results indicate development of a robust macrocyclic chelator that responds to various types of analytes. It is suitable for further structural optimizations which improve the physico-chemical and biokinetic properties of the resulting SCA. Ultimately, it leads to potent sensor molecules that can serve as MRI markers in functional imaging studies for monitoring important biological processes.