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Dual-frequency MRI contrast agents for visualization of biological processes

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Angelovski,  Goran
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

Angelovski, G. (2014). Dual-frequency MRI contrast agents for visualization of biological processes. In 247th ACS National Meeting and Exposition: Chemistry and Materials for Energy.


Cite as: http://hdl.handle.net/21.11116/0000-0000-FE65-1
Abstract
Magnetic resonance imaging (MRI) is one of the most important tools in clinical diagnostic and biological research. Lately, the development of 19F based MRI methods has been receiving increased attention due to its ability to overcome specific drawbacks associated with standard 1H MRI techniques. When combined, 1H and 19F MRI provide the opportunity to generate complementary information by using common expertise and instrumentation. We prepared a series of macrocyclic, fluorine-containing aryl-phosphonates and a range of their complexes with paramagnetic and diamagnetic ions. We also investigated various physico-chemical properties of the obtained molecules using a number of techniques. Thermodynamic and kinetic stability studies render them suitable for further in vivo characterization. The complexes exhibit high proton longitudinal relaxivities while displaying an increase in 19F relaxation rates which are favourable for 19F MRI experiments. Their potential was finally examined in the respective MRI phantom experiments. Subsequently, responsive complexes that contain Ca2+ chelator in between paramagnetic and fluorine-containing moieties are prepared. Favourably, they are capable of reporting the changes in Ca2+ concentrations simultaneously by 1H and 19F MRI. Extensive studies revealed mechanisms which underlie the intramolecular changes triggered by Ca2+, and are responsible for the alternation of MRI signals at both frequencies. A new generation of dual-frequency probes suitable for both 1H and 19F MRI opens novel perspectives in MRI. Agents with high longitudinal relaxivity at 1H, and enhanced relaxation rates at 19F frequency, respectively, allow gathering of critical information simultaneously with two different MRI methods. The responsive dual-frequency agents hold great promise for development of novel methods to successfully assess Ca2+ in living organisms and study essential physiological processes. The ability to observe its concentration changes in a non-invasive fashion would be of paramount importance for MRI methodology advancements and biomedical research in general.