Serial monitoring of human systemic and xenograft models of leukemia using a novel vascular disrupting agent. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Movement
  • Genes, Reporter
  • HL-60 Cells
  • Humans
  • Luminescent Measurements
  • Mice
  • Transduction, Genetic
  • Tumor Burden
  • Xenograft Model Antitumor Assays

MeSH Major

  • Antineoplastic Agents
  • Cell Tracking
  • Diphosphates
  • Leukemia
  • Stilbenes

abstract

  • Advances in the treatment of acute leukemia have resulted in significantly improved remission rates, although disease relapse poses a significant risk. By utilizing sensitive, non-invasive imaging guidance, detection of early leukemic infiltration and the extent of residual tumor burden after targeted therapy can be expedited, leading to more efficient treatment planning. We demonstrated marked survival benefit and therapeutic efficacy of a new-generation vascular disrupting agent, combretastatin-A1-diphosphate (OXi4503), using reporter gene-imaging technologies and mice systemically administered luc+ and GFP+ human leukemic cells (LCs). Before treatment, homing of double-transduced cells was serially monitored and whole-body cellular distributions were mapped using bioluminescence imaging (BLI). Imaging findings strongly correlated with quantitative GFP expression levels in solid organs/tissues, suggesting that the measured BLI signal provides a highly sensitive and reliable biomarker of tumor tissue burden in systemic leukemic models. Such optical technologies can thereby serve as robust non-invasive imaging tools for preclinical drug discovery and for rapidly screening promising therapeutic agents to establish potency, treatment efficacy and survival advantage. We further show that GFP+ HL-60 cells reside in close proximity to VE-cadherin- and CD31-expressing endothelial cells, suggesting that the perivascular niche may have a critical role in the maintenance and survival of LCs.

publication date

  • August 2012

has subject area

  • Animals
  • Antineoplastic Agents
  • Cell Movement
  • Cell Tracking
  • Diphosphates
  • Genes, Reporter
  • HL-60 Cells
  • Humans
  • Leukemia
  • Luminescent Measurements
  • Mice
  • Stilbenes
  • Transduction, Genetic
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4626450

Digital Object Identifier (DOI)

  • 10.1038/leu.2012.48

PubMed ID

  • 22343591

Additional Document Info

start page

  • 1771

end page

  • 1778

volume

  • 26

number

  • 8