Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

Int J Nanomedicine. 2012:7:3751-68. doi: 10.2147/IJN.S33139. Epub 2012 Jul 17.

Abstract

Background: Natural high-density lipoproteins (HDL) possess important physiological functions to the transport of cholesterol from the peripheral tissues to the liver for metabolic degradation and excretion in the bile.

Methods and results: In this work, we took advantage of this pathway and prepared two different gadolinium (Gd)-DTPA-labeled cholesterol-containing recombinant HDL nanoparticles (Gd-chol-HDL) and Gd-(chol)(2)-HDL as liver-specific magnetic resonance imaging (MRI) contrast agents. The reconstituted HDL nanoparticles had structural similarity to native HDL, and could be taken up by HepG2 cells via interaction with HDL receptors in vitro. In vivo MRI studies in rats after intravenous injections of 10 μmol gadolinium per kg of recombinant HDL nanoparticles indicated that both nanoparticles could provide signal enhancement in the liver and related organs. However, different T(1)-weighted image details suggested that they participated in different cholesterol metabolism and excretion pathways in the liver.

Conclusion: Such information could be highly useful to differentiate functional changes as well as anatomic differences in the liver. These cholesterol-derived contrast agents and their recombinant HDL preparations may warrant further development as a new class of contrast agents for MRI of the liver and related organs.

Keywords: apolipoprotein; contrast agent; gadolinium; high-density lipoprotein; liver; magnetic resonance imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Cholesterol / chemistry*
  • Cholesterol / pharmacokinetics
  • Contrast Media / chemical synthesis
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Gadolinium DTPA / chemistry*
  • Gadolinium DTPA / pharmacokinetics
  • Hep G2 Cells
  • Humans
  • Lipoproteins, HDL / chemistry*
  • Lipoproteins, HDL / pharmacokinetics
  • Liver / anatomy & histology*
  • Liver / metabolism
  • Liver / physiology
  • Magnetic Resonance Imaging / methods*
  • Magnetics
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacokinetics
  • Tissue Distribution

Substances

  • Contrast Media
  • Lipoproteins, HDL
  • Recombinant Proteins
  • Cholesterol
  • Gadolinium DTPA