Document Detail


A Method for Enhancing Cell-penetration of Gd<sup>3+</sup>-based MRI Contrast Agents by Conjugation with Hydrophobic Fluorescent Dyes.
MedLine Citation:
PMID:  21985057     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Gadolinium ion (Gd<sup>3+</sup>) complexes are commonly used as magnetic resonance imaging (MRI) contrast agents to enhance signals in <i>T</i><sub>1</sub>-weighted MR images. Recently, several methods to achieve cell-permeation of Gd<sup>3+</sup> complexes have been reported, but more general and efficient methodology is needed. In this report, we describe a novel method to achieve cell-permeation of Gd<sup>3+</sup> complexes by using hydrophobic fluorescent dyes as a cell-permeability-enhancing unit. We synthesized Gd<sup>3+</sup> complexes conjugated with boron dipyrromethene (<b>BDP-Gd</b>) and Cy7 dye (<b>Cy7-Gd</b>), and showed that these conjugates can be introduced efficiently into cells. To examine the relationship between cell-permeability and dye structure, we further synthesized a series of <b>Cy7-Gd</b> derivatives. On the basis of MR imaging, flow cytometry and ICP-MS analysis of cells loaded with <b>Cy7-Gd</b> derivatives, highly hydrophobic and non-anionic dyes were effective for enhancing cell-permeation of Gd<sup>3+</sup> complexes. Furthermore, the behavior of these <b>Cy7-Gd</b> derivatives was examined in mice. Thus, conjugation of hydrophobic fluorescent dyes appears to be an effective approach to improve the cell-permeability of Gd<sup>3+</sup> complexes, and should be applicable for further development of Gd<sup>3+</sup>-based MRI contrast agents.
Authors:
Takehiro Yamane; Kenjiro Hanaoka; Yasuaki Muramatsu; Keita Tamura; Yusuke Adachi; Yasushi Miyashita; Yasunobu Hirata; Tetsuo Nagano
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-11
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  -     ISSN:  1520-4812     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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