Tumor T1 Relaxation Time for Assessing Response to Bevacizumab Anti-Angiogenic Therapy in a Mouse Ovarian Cancer Model

PLoS One. 2015 Jun 22;10(6):e0131095. doi: 10.1371/journal.pone.0131095. eCollection 2015.

Abstract

Purpose: To assess whether T1 relaxation time of tumors may be used to assess response to bevacizumab anti-angiogenic therapy.

Procedures: 12 female nude mice bearing subcutaneous SKOV3ip1-LC ovarian tumors were administered bevacizumab (6.25ug/g, n=6) or PBS (control, n=6) therapy twice a week for two weeks. T1 maps of tumors were generated before, two days, and 2 weeks after initiating therapy. Tumor weight was assessed by MR and at necropsy. Histology for microvessel density, proliferation, and apoptosis was performed.

Results: Bevacizumab treatment resulted in tumor growth inhibition (p<0.04, n=6), confirming therapeutic efficacy. Tumor T1 relaxation times increased in bevacizumab treated mice 2 days and 2 weeks after initiating therapy (p<.05, n=6). Microvessel density decreased 59% and cell proliferation (Ki67+) decreased 50% in the bevacizumab treatment group (p<.001, n=6), but not apoptosis.

Conclusions: Findings suggest that increased tumor T1 relaxation time is associated with response to bevacizumab therapy in ovarian cancer model and might serve as an early indicator of response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Apoptosis
  • Bevacizumab / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Nude
  • Microvessels / pathology
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / therapy
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Bevacizumab