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

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.

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Dhingra, K1, 2, Author              
Mishra, A1, 2, Author              
Engelmann, J2, 3, Author              
Schüz, A1, 2, Author              
Canals, S, Author              
Pohmann, R, Author              
Beyerlein, M1, 2, Author              
Maier, ME, Author
Logothetis, NK1, 2, Author              
1Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497798              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497794              
3Former Department MRZ, Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_2528700              


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 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.


 Dates: 2010-02
 Publication Status: Published in print
 Pages: -
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 Identifiers: BibTex Citekey: DhingraMESCPBML2009
DOI: 10.1007/s11307-009-0251-y
 Degree: -


Title: 2009 World Molecular Imaging Congress (WMIC)
Place of Event: Montréal, Canada
Start-/End Date: 2009-09-23 - 2009-09-26

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Title: Molecular Imaging and Biology
Source Genre: Journal
Publ. Info: -
Pages: - Volume / Issue: 12 (Supplement 21) Sequence Number: J086 Start / End Page: S44 Identifier: -