Gd(III)-EPTPAC16, a new self-assembling potential liver MRI contrast agent: in vitro characterization and in vivo animal imaging studies

NMR Biomed. 2008 May;21(4):322-36. doi: 10.1002/nbm.1194.

Abstract

The recently reported amphiphilic chelate, [Gd(EPTPAC16)(H2O)]2-, forms supramolecular aggregates in aqueous solution by self-assembly of the monomers with a relaxometrically determined critical micellar concentration (CMC) of 0.34 mM. The effect of sonication on the aggregate size was characterized by dynamic light scattering and relaxometry, indicating the presence of premicellar aggregates and an overall decrease in aggregate size and polydispersity upon sonication, slightly below the CMC. [[153Sm](EPTPAC16)(H2O)]2- radiotracer was evaluated in vivo from gamma scintigraphy and biodistribution in Wistar rats. It was found to depend strongly on the sample concentration, below or above the CMC, and its sonication, in a way that correlates with the effect of the same factors on the size of the aggregates formed in solution. Below CMC, the very large aggregates of the [153Sm]3+ -labeled chelate were persistently and mainly taken up by the lungs, and also by the macrophage-rich liver and spleen. Sonication of this solution led to loss of the lung uptake. Above CMC, the metal chelate was mainly taken up by the liver, with very little uptake by the spleen and lungs. In vivo, dynamic contrast-enhanced (DCE)-MRI evaluation of the micellar [Gd(EPTPAC16)(H2O)]2- compound in Wistar rats showed a persistent hepatic positive-contrast effect in T1-weighted images, qualitatively similar to the clinically established Gd(III)-based hepatobiliary-selective agents. No enhancement effect was observed in the lungs because of the scarcity of mobile protons in this organ, despite the scintigraphic evidence of significant lung retention of the [153Sm]3+ -labeled chelate at concentrations below the CMC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacokinetics
  • Chelating Agents / pharmacology*
  • Contrast Media / chemistry
  • Contrast Media / pharmacokinetics
  • Contrast Media / pharmacology*
  • Imaging, Three-Dimensional / methods*
  • Light
  • Liver / diagnostic imaging
  • Liver / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Organ Specificity / drug effects
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / pharmacology*
  • Radionuclide Imaging
  • Rats
  • Rats, Wistar
  • Scattering, Radiation
  • Solutions
  • Sonication
  • Time Factors
  • Tissue Distribution / drug effects
  • Water

Substances

  • ((hydroxymethylhexadecanoyl ester)ethylenepropylene triaminepentaacetic acid)gadolinium(III)
  • Chelating Agents
  • Contrast Media
  • Organometallic Compounds
  • Solutions
  • Water