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Development of Bio-responsive Contrast Agents for Magnetic Resonance Imaging: Potential Applications of a Novel Precursor

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons83883

Dhingra,  K
Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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/persons83903

Engelmann,  J
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons84202

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

http://pubman.mpdl.mpg.de/cone/persons/resource/persons84751

Canals,  S
Max Planck Institute for Biological Cybernetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons84145

Pohmann,  R
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons83807

Beyerlein,  M
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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Citation

Dhingra, K., Mishra, A., Engelmann, J., Schüz, A., Canals, S., Pohmann, R., et al. (2009). Development of Bio-responsive Contrast Agents for Magnetic Resonance Imaging: Potential Applications of a Novel Precursor. Poster presented at 2009 World Molecular Imaging Congress (WMIC), Montréal, Canada.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0013-C329-6
Abstract
Magnetic resonance imaging (MRI) is one of the powerful imaging modality. To circumvent its low sensitivity, there has been a substantial interest on the development of the contrast agents. In the present scenario, there is a need to develop contrast agents which are target specific and can report the changes in the physiological environment around them. On the similar lines we are reporting here a novel precursor (tris-tert-Bu-(Z)-Ser-DO3A (Figure 1)). This precursor contains an amine and a carboxylate groups in an orthogonally protected condition, which allows their selective de-protection and coupling to different moieties. Out of the various possibilities, we explored two strategies of coupling that lead to a potential targeted CA and another CA with potential of tracing neuroanatomy in the brain. The special design of these agents not only provides the stability against their enzymatic degradation which is important for their in vivo applicability but also has the possibility to amplify its signal once recognized by the target site. This could be done by exploiting the biotin/strept(avidin) high affinity and the pretargeting strategy, which is well established in nuclear medicine. The CA when bound to avidin showed an enhancement in the relaxivity (r1 and r2) at 1.5T. A substantial increase of ≥1000 in r2 was observed at all magnetic fields studied (1.5T, 3T, 7T, 9.4T) while r1 showed an increase of 260 at 1.5T and an expected decrease with further increase of field strength. The relaxivity changes at 1.5T suggest the structural requirement of a CA to fit in to avidin and optimize the parameters determining relaxivity of the complex matches well with our synthesized agent. Using the same precursor, we have also synthesized a CA which can potentially be used for tracing the neuronal tracks in the brain. Biocytin was used as the basic tracer. Coupling an MR detectable moiety to a well known neuroanatomical tracer would open up new possibilities to noninvasively study the neuronal networks by MRI.