Document Detail


Cell-permeable MR contrast agents with increased intracellular retention.
MedLine Citation:
PMID:  18803414     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Magnetic resonance imaging (MRI) is a technique used in both clinical and experimental settings to produce high-resolution images of opaque organisms without ionizing radiation. Currently, MR imaging is augmented by contrast agents, and the vast majority these small molecule Gd(III) chelates are confined to the extracellular regions. As a result, contrast agents are confined to vascular regions reducing their ability to provide information about cell physiology or molecular pathology. We have shown that polypeptides of arginine have the capacity to transport Gd(III) contrast agents across cell membranes. However, this transport is not unidirectional, and once inside the cell, the arginine-modified contrast agents efflux rapidly, decreasing the intracellular Gd(III) concentration and corresponding MR image intensity. By exploiting the inherent disulfide reducing environment of cells, thiol compounds, Gd(III)-DOTA-SS-Arg 8 and Gd(III)-DTPA-SS-Arg 8, are cleaved from their cell-penetrating peptide transduction domains upon cell internalization. This reaction prolongs the cell-associated lifetime of the chelated Gd(III) by cleaving it from the cell transduction domain.
Authors:
Paul J Endres; Keith W MacRenaris; Stefan Vogt; Thomas J Meade
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-09-20
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  19     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-15     Completed Date:  2008-12-16     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2049-59     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Chelating Agents / chemistry
Contrast Media / chemical synthesis,  metabolism*
Disulfides / chemistry
Gadolinium / chemistry
Intracellular Space / metabolism*
Magnetic Resonance Imaging
Mice
Microscopy, Fluorescence
Organometallic Compounds / chemical synthesis,  diagnostic use*,  metabolism*
Permeability
Synchrotrons
X-Rays
Grant Support
ID/Acronym/Agency:
1 P50 NS054278-01/NS/NINDS NIH HHS; 1 S10 RR13880-01/RR/NCRR NIH HHS; 5 U54 CA119341-02/CA/NCI NIH HHS; P50 NS054287/NS/NINDS NIH HHS; P50 NS054287-019002/NS/NINDS NIH HHS; R01 EB005866/EB/NIBIB NIH HHS; R01 EB005866-01/EB/NIBIB NIH HHS; S10 RR013880-01/RR/NCRR NIH HHS; U54 CA119341/CA/NCI NIH HHS; U54 CA119341-02/CA/NCI NIH HHS; U54 CA119341-040003/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Chelating Agents; 0/Contrast Media; 0/Disulfides; 0/Organometallic Compounds; AU0V1LM3JT/Gadolinium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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