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Aryl Phosphonate-appended macrocyclic lanthanide complexes for application in bimodal imaging

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Placidi,  MP
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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Engelmann,  J
Department High-Field Magnetic Resonance, 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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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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Citation

Placidi, M., Engelmann, J., Logothetis, N., & Angelovski, G. (2011). Aryl Phosphonate-appended macrocyclic lanthanide complexes for application in bimodal imaging. Poster presented at 2011 World Molecular Imaging Congress (WMIC 2011), San Diego, CA, USA.


Cite as: http://hdl.handle.net/21.11116/0000-0001-9950-8
Abstract
Lanthanide complexes have unique physical properties making them suitable for applications in both luminescence and magnetic resonance imaging. Specifically, a mixture of lanthanide complexes from the same ligand can display identical biodistribution while exhibiting distinct optical and magnetic properties. We designed and synthesized a series of four ligand systems appended with an aryl phosphonate arm, whose solution-state properties accommodate the requirements of both imaging modalities. With the addition of Gd3+ and Tb3+, we obtained four Gd3+ complexes and four analogous Tb3+ complexes. The Gd3+ complexes displayed significantly higher relaxivities than those of commercially available agents and other phosphonate-appended macrocyclic complexes. Their efficacy was maintained in a model extracellular environment (DMEM), with only a modest loss in function. The Tb3+ complexes provided long-lived luminescence, with an inner sphere hydration number (q) ranging from 0.3 to 0.7. No significant effect on q was observed after the addition of biologically relevant quantities of either carbonate or phosphate, anions previously shown to inhibit the function of some contrast agents. Preliminary results were also obtained in cellulo. Phantom images of each of the Gd3+ complexes were recorded in the presence of 3T3 cells. Within the cell pellets, all the complexes displayed higher relaxivities than GdDOTA. Following incubation and washing, one of the complexes maintained a high relaxivity, implying a strong complex-cell interaction. The Investigated complexes hold great promise as contrast agents for bimodal imaging. They are effective in a range of media, including in the presence of cells. Moreover, through further synthetic modifications, these agents could be used in targeted cellular imaging.