A molecular imaging paradigm to rapidly profile response to angiogenesis-directed therapy in small animals

John Virostko, Jingping Xie, Dennis E. Hallahan, Carlos L. Arteaga, John C. Gore, H. Charles Manning

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Purpose: The development of novel angiogenesis-directed therapeutics is hampered by the lack of non-invasive imaging metrics capable of assessing treatment response. We report the development and validation of a novel molecular imaging paradigm to rapidly assess response to angiogenesis-directed therapeutics in preclinical animal models. Procedures: A monoclonal antibody-based optical imaging probe targeting vascular endothelial growth factor receptor-2 (VEGFR2) expression was synthesized and evaluated in vitro and in vivo via multispectral fluorescence imaging. Results: The optical imaging agent demonstrated specificity for the target receptor in cultured endothelial cells and in vivo. The agent exhibited significant accumulation within 4T1 xenograft tumors. Mice bearing 4T1 xenografts and treated with sunitinib exhibited both tumor growth arrest and decreased accumulation of NIR800-αVEGFR2ab compared to untreated cohorts (p = 0.0021). Conclusions: Molecular imaging of VEGFR2 expression is a promising non-invasive biomarker for assessing angiogenesis and evaluating the efficacy of angiogenesis-directed therapies.

Original languageEnglish (US)
Pages (from-to)204-212
Number of pages9
JournalMolecular Imaging and Biology
Volume11
Issue number3
DOIs
StatePublished - Jan 9 2009

Keywords

  • Angiogenesis
  • Biomarker
  • Molecular imaging
  • Multispectral fluorescence
  • Near-infrared fluorescence
  • Optical imaging
  • Sunitinib
  • Tyrosine kinase inhibitor
  • VEGF
  • VEGFR2

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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