title: Assessment of angiogenesis: implications for ultrasound imaging.
abstract: In this paper, the fundamentals of tumor angiogenesis and the implications for ultrasound imaging will be described. Twenty-eight athymic nude mice were implanted with the human melanoma cell lines DB-1 or MW-9 (14 mice/group). Ultrasound contrast agents were injected in the tail veins. Power Doppler and pulse inversion harmonic imaging (PI-HI) was performed (in real time and intermittently). Ultrasound results were compared to immunohistochemical stains for endothelial cells (CD31), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2). Linear regression analysis indicated statistically significant correlations between percent area stained with COX-2 and with VEGF relative to power Doppler (p<0.05) and intermittent PI-HI (p<0.05) measures of tumor neovascularity in the MW-9 and the DB-1 mice, respectively. Preliminary results from a human trial of the anti-angiogenic drug Angiostatin (Entremed, Rockville, MD) showed tumor volumes increased in two patients, while the vascularity remained virtually unchanged. Conversely, in three patients with diminished tumor volumes vascularity increased by 38%. In conclusion, contrast enhanced ultrasound imaging of tumor neovascularity may provide noninvasive markers of angiogenesis and may become a useful tool for monitoring anti-angiogenic therapies in vivo.
authors.affiliation: Department of Radiology, Division of Diagnostic Ultrasound, Suite 763J, Main Building, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA 19107, USA. flemming.forsberg@jefferson.edu
authors.forename: F
authors.initials: F
authors.lastname: Forsberg
authors.forename: R J
authors.initials: RJ
authors.lastname: Ro
authors.forename: M
authors.initials: M
authors.lastname: Potoczek
authors.forename: J B
authors.initials: JB
authors.lastname: Liu
authors.forename: C R B
authors.initials: CR
authors.lastname: Merritt
authors.forename: K M
authors.initials: KM
authors.lastname: James
authors.forename: A P
authors.initials: AP
authors.lastname: Dicker
authors.forename: L N
authors.initials: LN
authors.lastname: Nazarian
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D043168:Angiostatins / Q000494:pharmacology; D000818:Animals; D003287:Contrast Media; D051546:Cyclooxygenase 2; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D016014:Linear Models; D008546:Melanoma, Experimental / Q000097:blood* / Q000098:blood supply / Q000000981:diagnostic imaging; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D014407:Tumor Cells, Cultured; D014463:Ultrasonography; D018608:Ultrasonography, Doppler; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D007527:Isoenzymes; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D043168:Angiostatins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases