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Poster

PyroEGTA-Derived Metal Ion Responsive Probes for MRI

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons84084

Mishra,  A
Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons84063

Logothetis,  NK
Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Zitation

Mishra, A., Parker, D., & Logothetis, N. (2010). PyroEGTA-Derived Metal Ion Responsive Probes for MRI. Poster presented at 2010 World Molecular Imaging Congress (WMIC), Kyoto, Japan.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0013-BE88-2
Zusammenfassung
For proper brain development and function, a critical relationship exists between the elements calcium, magnesium and zinc. Their deficiency or excess accumulation in the body may cause several diseases. Thus, in vivo determination of the distribution of these metal ions is extremely desirable. Recently, advances have been made in the design of responsive probes sensitive to certain metal ions.1,2 The use of MRI to detect fluctuations in the concentration of vital metal ions has recently received much attention. However, there is still a need to develop more sensitive and selective probes for biologically important metal ions. Here, we describe two structurally different pyro-EGTA derived lanthanide complexing DO3A probes, which respond to changes in Ca2+ and Zn2+ concentrations at physiological pH. The complex [LnL1] contains a LnDO3A moiety coupled to a carbomethoxy group of the pyroEGTA derivative [2,2'-(2-(2-(carboxymethoxy)phenoxy)ethylazanediyl)diacetic acid] via an amide bond. This complex possesses six coordination sites suitable for sensing small ionic radii (Zn2+, Mg2+) metal ions. The complex [LnL2] contains eight coordination sites, appropriate for larger ions such as Ca2+. Changes in relaxivity were monitored following addition of appropriate divalent metal ions. In vitro relaxivity measurements were performed at physiological pH in competitive aqueous media at 1.4T and 37oC. [GdL1] showed a 66 relaxivity change on addition of Zn2+. This molecule responded selectively to Zn2+ rather than Ca2+ and Mg2+. [GdL2] showed a relaxivity change of 64 upon addition of Ca2+ and was insensitive to other added divalent ions in the millimolar range. Parallel luminescence titrations were also undertaken with [EuL1] and [EuL2] in the presence and absence of various divalent ions. Changes in europium emission spectra and the modulation of q values were observed upon addition of Zn2+ and Ca2+ for [EuL1] and [EuL2], respectively. Thus, enhancements in hydration numbers were found were, in accord with the variations in relaxivity. 1. Que E. L. et al, Chem Soc Rev. 2010;39 (1):51-60. 2. Reany O. et al, J. Chem. Soc. Perkin. Trans. 2, 2000, 1819-1831.