Reduction of vascular and permeable regions in solid tumors detected by macromolecular contrast magnetic resonance imaging after treatment with antiangiogenic agent TNP-470

Purpose: The availability of noninvasive techniques to detect the effects of antiangiogenic agents is critically important for optimizing treatment of cancer with these agents. Magnetic resonance imaging (MRI) is one such noninvasive technique that is routinely used clinically. Experimental Design: In this study, we have evaluated the use of MRI of the intravascular contrast agent albumin-GdDTPA to detect the effects of the antiangiogenic agent TNP-470 on the vascular volume and permeability of the MatLyLu prostate cancer model. Results: TNP-470-treated tumors demonstrated a significant decrease of vascular volume, as well as a significant reduction in vascular and permeable regions, compared with volume-matched control tumors. Although the fractional volume of permeable regions in the tumor decreased, the average value of tumor permeability did not decrease significantly. This was attributable to increase in permeability in some regions of the tumor. These regions were mostly associated with low vascular volume. ELISA assays of control and treated MatLyLu tumors also detected a significant increase of vascular endothelial growth factor in the TNP-470-treated tumors. Conclusion: MRI detected significant changes in tumor vascular characteristics after treatment with TNP-470.