Dynamic bioluminescence and fluorescence imaging of the effects of the antivascular agent Combretastatin-A4P (CA4P) on brain tumor xenografts

Li Liu, Ralph P. Mason, Barjor Gimi

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Combretastatin A-4 (CA4) is a natural product isolated from Combretum caffrum that inhibits tubulin polymerization by binding to the colchicine-binding site. A corresponding water soluble pro-drug (referred to as CA4P), has undergone extensive clinical trials and has been evaluated in pre-clinical studies using multiple modalities. We previously reported a novel assay based on dynamic bioluminescent imaging to assess tumor vascular disruption and now present its application to assessing multiple tumors simultaneously. The current study evaluated the vascular-disrupting activity of CA4P on subcutaneous 9L rat brain tumor xenografts in mice using dynamic bioluminescence imaging. A single dose of CA4P (120 mg/kg, intraperitoneally) induced rapid, temporary tumor vascular shutdown revealed by a rapid and reproducible decrease of light emission from luciferase-expressing 9L tumors following administration of luciferin as a substrate. A time-dependent reduction of tumor perfusion after CA4P treatment was confirmed by immunohistological assessment of the perfusion marker Hoechst 33342 and the tumor vasculature marker CD31. The vasculature showed distinct recovery within 24 h post therapy. Multiple tumors behaved similarly, although a size dependent vascular inhibition was observed. In conclusion, CA4P caused rapid, temporary tumor vascular shutdown and led to reduction of tumor perfusion in rat brain tumor xenografts and the multiple tumor approach should lead to more efficient studies requiring fewer animals and greater consistency.

Original languageEnglish (US)
Pages (from-to)462-469
Number of pages8
JournalCancer Letters
Volume356
Issue number2
DOIs
StatePublished - Jan 28 2015

Keywords

  • Bioluminescence imaging (BLI)
  • Brain tumor
  • CA4P
  • Fluorescence imaging (FLI)
  • Vascular disrupting agent (VDA)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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