Lipid nanocapsules loaded with rhenium-188 reduce tumor progression in a rat hepatocellular carcinoma model

PLoS One. 2011 Mar 7;6(3):e16926. doi: 10.1371/journal.pone.0016926.

Abstract

Background: Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC(188)Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC(188)Re-SSS in a chemically induced hepatocellular carcinoma rat model.

Methodology/principal findings: Animals were treated with an injection of LNC(188)Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and (188)Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC(188)Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC(188)Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process.

Conclusions/significance: Overall, these results demonstrate that internal radiation with LNC(188)Re-SSS is a promising new strategy for hepatocellular carcinoma treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / pathology*
  • Catheterization
  • Disease Models, Animal
  • Disease Progression*
  • Kinetics
  • Lipids / chemistry*
  • Lipids / pharmacokinetics
  • Liver Neoplasms / blood
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Nanocapsules / chemistry*
  • Radioisotopes
  • Rats
  • Rats, Wistar
  • Rhenium / chemistry*
  • Rhenium / pharmacokinetics
  • Survival Analysis
  • Tissue Distribution
  • Transaminases / metabolism
  • Tumor Burden
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Lipids
  • Nanocapsules
  • Radioisotopes
  • Vascular Endothelial Growth Factor A
  • Rhenium
  • Transaminases