Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma

Tatiana Abakumova, Maxim Abakumov, Sergey Shein, Pavel Chelushkin, Dmitry Bychkov, Vladimir Mukhin, Gaukhar Yusubalieva, Nadezhda Grinenko, Alexander Kabanov, Natalia Nukolova, Vladimir Chekhonin

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM-1 s-1 at 7 T) than the commercial agent Magnevist® (3.4 mM-1 s-1). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalContrast Media and Molecular Imaging
Issue number1
StatePublished - Jan 1 2016
Externally publishedYes


  • Cellular targeting
  • Connexin 43
  • Glioma
  • MRI
  • T contrast agent
  • Targeted imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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