Manganese Complex of Ethylenediaminetetraacetic Acid (EDTA)-Benzothiazole Aniline (BTA) Conjugate as a Potential Liver-Targeting MRI Contrast Agent

J Med Chem. 2017 Apr 13;60(7):2993-3001. doi: 10.1021/acs.jmedchem.6b01799. Epub 2017 Mar 22.

Abstract

A novel manganese(II) complex based on an ethylenediaminetetraacetic acid (EDTA) coordination cage bearing a benzothiazole aniline (BTA) moiety (Mn-EDTA-BTA) was designed and synthesized for use as a liver-specific MRI contrast agent with high chelation stability. In addition to forming a hydrophilic, stable complex with Mn2+, this new Mn chelate was rapidly taken up by liver hepatocytes and excreted by the kidneys and biliary system. The kinetic inertness and R1 relaxivity of the complex were much higher than those of mangafodipir trisodium (MnDPDP), a clinically approved liver-specific MRI contrast agent. The diagnostic utility of this new Mn complex in MRI was demonstrated by high-sensitivity tumor detection in an animal model of liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemistry*
  • Aniline Compounds / pharmacokinetics
  • Animals
  • Benzothiazoles / chemistry*
  • Benzothiazoles / pharmacokinetics
  • Cell Line, Tumor
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacokinetics
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Coordination Complexes / analogs & derivatives
  • Coordination Complexes / pharmacokinetics
  • Edetic Acid / chemistry*
  • Hepatocytes / pathology
  • Humans
  • Liver / cytology
  • Liver / diagnostic imaging*
  • Liver / pathology
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / pathology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Manganese / chemistry*
  • Manganese / pharmacokinetics
  • Mice, Inbred BALB C
  • Mice, Nude

Substances

  • Aniline Compounds
  • Benzothiazoles
  • Chelating Agents
  • Contrast Media
  • Coordination Complexes
  • Manganese
  • Edetic Acid