Pharmacokinetics of Gd(DO3A-Lys) and MR imaging studies in an orthotopic U87MG glioma tumor model

Contrast Media Mol Imaging. 2015 May-Jun;10(3):237-44. doi: 10.1002/cmmi.1634. Epub 2015 Jan 22.

Abstract

Pharmacokinetics of Gd(DO3A-Lys), a macrocyclic gadolinium-based magnetic resonance imaging (MRI) contrast agent functionalized with a lysine derivative, was studied in Wistar rats. Kinetic data were fitted using a two-compartment model and revealed Gd(DO3A-Lys) to have a distribution half-life, t1/2 (α), of 1.3 min, an elimination half-life, t1/2 (β), of 24.9 min and a large volume of distribution, VD , of 0.49 L/kg indicative of the agent being able to rapidly distribute into tissues and organs. Contrast-enhanced magnetic resonance angiography (CE-MRA) in an orthotopic U87MG glioma mouse model demonstrated considerable enhancement of both the tumor and surrounding vasculature after intravenous administration of Gd(DO3A-Lys). Applying dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the glioma of different sizes further showed distinct uptake characteristics and patterns of enhancement, which suggests the potential for differentiating changes at different stages of tumor growth. Our results indicate that Gd(DO3A-Lys) could be a promising candidate for glioma MR imaging.

Keywords: Gadolinium chelate; contrast agent; magnetic resonance imaging (MRI); orthotopic glioma model; pharmacokinetics; tumor diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / chemistry
  • Contrast Media / pharmacokinetics*
  • Disease Models, Animal
  • Gadolinium / chemistry
  • Gadolinium / pharmacokinetics*
  • Glioma / blood supply*
  • Glioma / diagnosis
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics*
  • Lysine / chemistry
  • Magnetic Resonance Angiography / methods*
  • Male
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacokinetics
  • Rats
  • Rats, Wistar

Substances

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