Magnetic resonance imaging identifies early effects of sunitinib treatment in human melanoma xenografts

J Exp Clin Cancer Res. 2013 Nov 19;32(1):93. doi: 10.1186/1756-9966-32-93.

Abstract

Background: Antiangiogenic treatment may change the tumor microenvironment and hence influence the effect of conventional therapies. The potential of diffusion weighted magnetic resonance imaging (DW-MRI) and dynamic contrast enhanced MRI (DCE-MRI) in assessing microenvironmental effects of sunitinib treatment was investigated in this preclinical study.

Methods: Sunitinib-treated and untreated A-07 tumors were subjected to DW-MRI and DCE-MRI, and parametric images of ADC and Ktrans were produced. Microvascular density, hypoxic fraction, and necrotic fraction were assessed from immunohistochemical preparations, and tumor interstitial fluid pressure (IFP) was assessed with probe measurement.

Results: Sunitinib-treated tumors showed reduced microvascular density, increased hypoxic fraction, increased necrotic fraction, increased ADC, and reduced Ktrans, but did not differ from untreated tumors in growth rate and IFP.

Conclusions: Sunitinib treatment affected the tumor microenvironment without affecting tumor size. DW-MRI and DCE-MRI were sensitive to the sunitinib-induced changes in the tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Female
  • Humans
  • Indoles / pharmacology*
  • Magnetic Resonance Imaging / methods
  • Melanoma, Amelanotic / diagnosis*
  • Melanoma, Amelanotic / drug therapy*
  • Melanoma, Amelanotic / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pyrroles / pharmacology*
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Sunitinib
  • Tumor Microenvironment
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Sunitinib