Method for enhancing cell penetration of Gd 3+-based MRI contrast agents by conjugation with hydrophobic fluorescent dyes

Takehiro Yamane, Kenjiro Hanaoka, Yasuaki Muramatsu, Keita Tamura, Yusuke Adachi, Yasushi Miyashita, Yasunobu Hirata, Tetsuo Nagano

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Gadolinium ion (Gd 3+) complexes are commonly used as magnetic resonance imaging (MRI) contrast agents to enhance signals in T 1-weighted MR images. Recently, several methods to achieve cell-permeation of Gd 3+ 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 3+ complexes by using hydrophobic fluorescent dyes as a cell-permeability-enhancing unit. We synthesized Gd 3+ complexes conjugated with boron dipyrromethene (BDP-Gd) and Cy7 dye (Cy7-Gd), 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 Cy7-Gd derivatives. On the basis of MR imaging, flow cytometry, and ICP-MS analysis of cells loaded with Cy7-Gd derivatives, highly hydrophobic and nonanionic dyes were effective for enhancing cell permeation of Gd 3+ complexes. Furthermore, the behavior of these Cy7-Gd derivatives was examined in mice. Thus, conjugation of hydrophobic fluorescent dyes appears to be an effective approach to improve the cell permeability of Gd 3+ complexes, and should be applicable for further development of Gd 3+-based MRI contrast agents.

Original languageEnglish
Pages (from-to)2227-2236
Number of pages10
JournalBioconjugate Chemistry
Issue number11
Publication statusPublished - 2011 Nov 16
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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