In vivo assessment of vascular endothelial growth factor‐induced angiogenesis

To determine whether vascular endothelial growth factor (VEGF)‐induced tumor microvascularity is detectable by in vivo NMR imaging, an experimental study was conducted in nude mice. Human breast cancer cells (MCF‐7) and MCF‐7 cells stably transfected with the cDNA for the VEGF165 isoform (MV165) were grown in nude mice and models were characterized by RT‐PCR, Western blotting, ELISA, immunohistochemistry and NMR imaging using a novel synthetic protected graft copolymer (PGC) as a vascular probe. MV165 tumors showed a 1.6‐fold higher microvascular density by histology. Both tumors showed identical MR signal intensities on non‐contrast and Gd‐DTPA enhanced images. PGC enhanced MR imaging of tumoral vascular volume fraction (VVF), however, revealed significant differences between the 2 tumor types (MV165: 8.9 ± 2.1; MCF‐7: 1.7 ± 0.5; p < 0.003), as expected from histology. VVF changes were more heterogeneous in the MV165 model both among tumors as well as within tumors as determined 3‐dimensionally at submillimeter resolutions. Our results have potential applications for non‐invasive assessment of angiogenesis by in vivo imaging and for clinical monitoring during angiogenic therapies. Int. J. Cancer 83:798–802, 1999. © 1999 Wiley‐Liss, Inc.