Dynamic contrast-enhanced magnetic resonance imaging at 1.5 Tesla with gadopentetate dimeglumine to assess the angiostatic effects of anginex in mice

Q. G. De Lussanet, R. G.H. Beets-Tan, W. H. Backes, D. W.J. Van Der Schaft, J. M.A. Van Engelshoven, K. H. Mayo, A. W. Griffioen

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31 Scopus citations

Abstract

The purpose of this study was to evaluate the effects of anginex on tumour angiogenesis assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on a clinical 1.5 Tesla MR system and with the clinically available contrast agent gadopentetate dimeglumine. C57BL/6 mice carrying B16F10 melanomas were treated with anginex, TNP-470 or saline. Tumour growth curves and microvessel density (MVD) were recorded to establish the effects of treatment. DCE-MRI was performed on day 16 after tumour inoculation, and the endothelial transfer coefficients of the microvessel permeability surface-area product (KPS) were calculated using a two-compartment model. Both anginex and TNP-470 resulted in smaller tumour volumes (P<0.0001) and lower MVD (P <0.05) compared to saline. Treatment with anginex resulted in a 64% reduction (P<0.01) of tumour KPS and TNP-470 resulted in a 44% reduction (P=0.17), compared to saline. DCE-MRI with a clinically available, small-molecular contrast agent can therefore be used to evaluate the angiostatic effects of anginex and TNP-470 on tumour angiogenesis.

Original languageEnglish (US)
Pages (from-to)1262-1268
Number of pages7
JournalEuropean Journal of Cancer
Volume40
Issue number8
DOIs
StatePublished - May 2004

Bibliographical note

Funding Information:
This work was supported by research grants from the National Institutes of Health (CA-96090), the U.S. Department of Defence (Army) (DA/DAMD17-99-1-9564), the Dutch Cancer Society (UM 2001-2529) and ActiPep Biotechnology, Inc. We are grateful to Denisha Walek of the Microchemical Facility of the University of Minnesota, for expertise in the synthesis of peptides.

Keywords

  • Anginex
  • Angiogenesis inhibitors
  • Angiostatic agents
  • B16 melanoma
  • Gadopentetate dimeglumine
  • Gd-DTPA
  • MRI
  • MRI, functional
  • Mice
  • Microvascular permeability
  • TNP-470

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