Gadolinium Complex of 1,4,7,10-Tetraazacyclododecane-1,4,7-trisacetic Acid (DO3A)-Ethoxybenzyl (EOB) Conjugate as a New Macrocyclic Hepatobiliary MRI Contrast Agent

J Med Chem. 2017 Jun 22;60(12):4861-4868. doi: 10.1021/acs.jmedchem.7b00060. Epub 2017 May 31.

Abstract

We report the synthesis of a macrocyclic Gd chelate based on a 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) coordinationn cage bearing an ethoxybenzyl (EOB) moiety and discuss its use as a T1 hepatobiliary magnetic resonance imaging (MRI) contrast agent. The new macrocyclic liver agent shows high chelation stability and high r1 relaxivity compared with linear-type Gd chelates, which are the current clinically approved liver agents. Our macrocyclic, liver-specific Gd chelate was evaluated in vivo through biodistribution analysis and liver MRI, which demonstrated its high tumor detection sensitivity and suggested that the new Gd complex is a promising contrast agent for liver cancer imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacokinetics
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics*
  • Gadolinium / chemistry*
  • HEK293 Cells
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Humans
  • Kinetics
  • Liver / diagnostic imaging*
  • Liver Neoplasms, Experimental / diagnostic imaging
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice, Inbred ICR
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid
  • Chelating Agents
  • Contrast Media
  • Heterocyclic Compounds, 1-Ring
  • Gadolinium