Gd-complexes of DTPA-bis(amide) conjugates of tranexamic acid and its esters with high relaxivity and stability for magnetic resonance imaging

Dalton Trans. 2008 Apr 28:(16):2199-206. doi: 10.1039/b719440d. Epub 2008 Mar 13.

Abstract

The synthesis and the characterization of a series of DTPA-bis(amide) conjugates of tranexamic acid (L1), its esters (L2-L6), and their Gd(III) complexes of the type [Gd(L)(H2O)].nH2O (L = L1-L6) are described. Except for the case of , all Gd-complexes exhibit greatly enhanced R1 relaxivity. Highest R1 reaches up to 12.9 mM(-1) s(-1) for [Gd(L2)(H2O)]. Such high relaxivity is reflected in the intensity enhancement of the in vivo MRI study on H-ras transgenic mice bearing hepatic tumor when employing [Gd(L2)(H2O)] as an MRI contrast agent. Thermodynamic stability constants, conditional stability constants, and the pM values demonstrate higher stability of [Gd(L)(H2O)].nH2O (L =L1-L6) than Omniscan under physiological conditions. The MTT assay performed on these complexes reveals cytotoxicity as low as that for Omniscan in the concentration range required to obtain intensity enhancement in the in vivo MRI study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Chick Embryo
  • Contrast Media / chemical synthesis*
  • Contrast Media / chemistry
  • Contrast Media / pharmacology
  • Cornea / cytology
  • Drug Stability
  • Esters / chemistry*
  • Gadolinium DTPA / chemistry*
  • Liver Neoplasms, Experimental / diagnosis*
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Transgenic
  • Molecular Structure
  • Toxicity Tests
  • Tranexamic Acid / chemistry*

Substances

  • Amides
  • Contrast Media
  • Esters
  • Tranexamic Acid
  • Gadolinium DTPA