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Unusual Calcium Sensitivity of Aminobis(methylenephosphonate)-Containing MRI Contrast Agents

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Mamedov,  I
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
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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Logothetis,  NK
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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Citation

Mamedov, I., Henig, J., Angelovski, G., Fouskova, P., Tóth, É., Logothetis, N., et al. (2009). Unusual Calcium Sensitivity of Aminobis(methylenephosphonate)-Containing MRI Contrast Agents. In G. Meyer, & I. Pantenburg (Eds.), 7th International Conference on f-Elements (7 ICfE) incorporating XXII. Tage der Seltenen Erden (Terrae Rarae 2009) (pp. 75). Bornheim, Germany: NWT-Verlag.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0013-C34B-9
Abstract
Magnetic resonance imaging (MRI) is currently one of the most powerful tools in medical diagnosis and is strongly related to the development of paramagnetic contrast agents. These are commonly based on trivalent gadolinium which has the strong influence on the relaxation of surrounding water protons. The objective of our study is to develop a MRI-d etectable molecule for tracking the modulation in calcium, which is an excellent marker tightly linked to brain activation. Recently, our group synthesized and investigated the properties of several Ca-sensitive, smart contrast agents (SCA) [1,2]. Using a different approach than previously reporte d, we prepared a new series of potential DO3A-based SCAs, having alkylaminobis(methylenephosphonate) side chains. Four different ligands with propyl, butyl, pentyl or hexyl linkers between the aminobi s(methylenephosphonates) and DO3A were prepared and the physico-chemical properties of their Gd(III) and Eu(III) complexes were studied. Significant differences were observed in the longitudinal relaxivity ( r 1 ) response of studied Gd(III)-complexes towards Ca(II) being dependant on th e aliphatic side chain length. No changes in r 1 of the propyl analogue were found over the whole span of Ca(II) concentration whereas the decrease to 61% of the initial r 1 value was observed for the complex bearing hexyl linker. Additional studies, including various NMR and luminescence spectroscopy methods, were performed on these systems in order to understand th eir unusual behavior. The results indicate very unique coordination properties of these complexes leading to a specific triggering mechanism responsible for the r 1 changes. These findings will be helpful fo r future design of novel SCA classes, as well as for their application in MRI.