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.
Lewin
M
M
Center for Molecular Imaging Research, Massachusetts General Hospital/Harvard Medical School, Charlestown 02129, USA.
Bredow
S
S
Sergeyev
N
N
Marecos
E
E
Bogdanov
A
A
Weissleder
R
R
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019786:Gadolinium DTPA