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  Novel Gd-Based Neuroanatomical Tract Tracers for Optical and Magnetic Resonance Imaging

Mishra, A., Dhingra, K., Mishra, R., Schüz, A., Logothetis, N., & Canals, S. (2008). Novel Gd-Based Neuroanatomical Tract Tracers for Optical and Magnetic Resonance Imaging. Poster presented at 2008 World Molecular Imaging Congress (WMIC), Nice, France.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-C775-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-8BA1-A
Genre: Poster

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WMIC-2008-Mishra.pdf (Abstract), 97KB
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Mishra, A1, 2, Author              
Dhingra, K1, 2, Author              
Mishra, R2, 3, Author              
Schüz, A1, 2, Author              
Logothetis, NK1, 2, Author              
Canals, S1, 2, Author              
Affiliations:
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: The advance of axonal tract-tracing has revolutionized neuroscience in the past three decades1. The elementary purpose of neuronal tract-tracing is to chart anatomical connections within the nervous system providing useful information on afferent and efferent connectivity in the brain. Biocytin is a classical neuroanatomical tract-tracer that is taken up by neurons and transported in both antero- and retrograde directions. Our aim was to develop non-toxic, efficient neuronal tracers that allow both, in vivo brain connectivity studies by means of MRI and postmortem-microscopic investigation in fixed tissue, in the same experimental animal. We have designed five novel biocytin-based neuroanatomical tract-tracers (L1-L5). In newly modified-biocytin (L1), propylamine is linked to amide of biocytin to make it tert-amide, which is stable to biotinidase degradation. The propylamine of L1was used as a linker to link, FITC as a fluorescent moiety (L2) or Gd-DOTA as MR detectable part (L3). L4 has an amide linkage between amine of GdDO3A-EA and carboxylate of biocytin while L5 consists of a novel precursor based on serine containing Gd-DO3A. This precursor has an amine and a carboxylate group available for coupling of biotin and l-lysine. In vivo histological experiments with L1 demonstrated an increased molecular stability compared with biocytin and excellent neuronal tract-tracing capabilities. In vitro efficiency of cell internalization of L2 into N18 neuroblastoma cells was demonstrated by fluorescence microscopy. In vitro MRI of L3-L5 with increasing concentrations of avidin were performed at 7T. The increase in R2 for L3-L5 (300-100 respectively) demonstrated strong binding of all tracers in the pocket of tetrameric avidin through biotin. The above studies and preliminary results reveal a new strategy for neuroanatomical tract-tracing, which combines the powerful spatial resolution of the conventional microscopic techniques with the whole brain tri-dimensional coverage and in vivo applicability of MRI.

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 Dates: 2008-09
 Publication Status: Published in print
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 Identifiers: BibTex Citekey: 5258
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Title: 2008 World Molecular Imaging Congress (WMIC)
Place of Event: Nice, France
Start-/End Date: 2008-09-10 - 2008-09-13

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Title: 2008 World Molecular Imaging Congress (WMIC)
Source Genre: Proceedings
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