title: The antiangiogenic effects of a vascular endothelial growth factor decoy receptor can be monitored in vivo using contrast-enhanced ultrasound imaging.
abstract: The development of antiangiogenic therapies has stimulated interest in noninvasive imaging methods to monitor response. We investigated whether the effects of a vascular endothelial growth factor decoy receptor (VEGF Trap, Regeneron Pharmaceuticals, Tarrytown, NY) could be monitored in vivo using contrast-enhanced ultrasonography (CEUS). Twenty nude mice (in two groups) were implanted with a human melanoma cell line (DB-1). The active group received VEGF Trap (4 × 25 mg/kg over 2 weeks), whereas the control group received an inactive protein. An ultrasound contrast agent was injected followed by power Doppler imaging (PDI) and pulse inversion harmonic imaging (PIHI; regular and intermittent). Specimens were sectioned in the same planes as the images and stained for endothelial cells (CD31), cyclooxygenase-2 (COX-2), VEGF, and hypoxia (Glut1). Measures of tumor vascularity obtained with the different imaging modes were compared to immunohistochemical markers of angiogenesis. Mean tumor volume was smaller in the active group than in the control group (656 ± 225 vs 1,160 ± 605 mm3). Overall, PDI and VEGF correlated (r  =  .34; p =  .037). Vascularity decreased from control to treated mice with intermittent PIHI, as did the expression of CD31 and COX-2 (p ≤ .02), whereas VEGF increased (p  =  .05). CEUS appears to allow in vivo monitoring of the antiangiogenic effects of VEGF Trap in the DB-1 human melanoma xenograft model.
authors.forename: Flemming
authors.initials: F
authors.lastname: Forsberg
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Ro
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Liu
authors.forename: See-Ying
authors.initials: SY
authors.lastname: Chiou
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Merton
authors.forename: Priscilla
authors.initials: P
authors.lastname: Machado
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.forename: Levon N
authors.initials: LN
authors.lastname: Nazarian
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D016014:Linear Models; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000494:pharmacology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D014463:Ultrasonography / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor