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.
Bibliographical noteFunding 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.
- Angiogenesis inhibitors
- Angiostatic agents
- B16 melanoma
- Gadopentetate dimeglumine
- MRI, functional
- Microvascular permeability