Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids

Angiogenesis. 2011 May;14(2):143-53. doi: 10.1007/s10456-010-9198-5. Epub 2011 Jan 12.

Abstract

Inflammation plays a prominent role in tumor growth. Anti-inflammatory drugs have therefore been proposed as anti-cancer therapeutics. In this study, we determined the anti-angiogenic activity of a single dose of liposomal prednisolone phosphate (PLP-L), by monitoring tumor vascular function and viability over a period of one week. C57BL/6 mice were inoculated subcutaneously with B16F10 melanoma cells. Six animals were PLP-L-treated and six served as control. Tumor tissue and vascular function were probed using MRI before and at three timepoints after treatment. DCE-MRI was used to determine K(trans), v(e), time-to-peak, initial slope and the fraction of non-enhancing pixels, complemented with immunohistochemistry. The apparent diffusion coefficient (ADC), T(2) and tumor size were assessed with MRI as well. PLP-L treatment resulted in smaller tumors and caused a significant drop in K(trans) 48 h post-treatment, which was maintained until one week after drug administration. However, this effect was not sufficient to significantly distinguish treated from non-treated animals. The therapy did not affect tumor tissue viability but did prevent the ADC decrease observed in the control group. No evidence for PLP-L-induced tumor vessel normalization was found on histology. Treatment with PLP-L altered tumor vascular function. This effect did not fully explain the tumor growth inhibition, suggesting a broader spectrum of PLP-L activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Contrast Media
  • Diffusion Magnetic Resonance Imaging
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Liposomes / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Microvessels / drug effects
  • Microvessels / pathology
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Prednisolone / analogs & derivatives*
  • Prednisolone / pharmacology
  • Prednisolone / therapeutic use

Substances

  • Angiogenesis Inhibitors
  • Contrast Media
  • Glucocorticoids
  • Liposomes
  • prednisolone phosphate
  • Prednisolone