The Antiangiogenic Effects of a Vascular Endothelial Growth Factor Decoy Receptor Can Be Monitored in Vivo Using Contrast-Enhanced Ultrasound Imaging

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 co...

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Main Authors: Flemming Forsberg, Raymond J. Ro, Andrew Marshall, Ji-Bin Liu, See-Ying Chiou, Daniel A. Merton, Priscilla Machado, Adam P. Dicker, Levon N. Nazarian
Format: Article
Language:English
Published: SAGE Publishing 2014-03-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2013.00073
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author Flemming Forsberg
Raymond J. Ro
Andrew Marshall
Ji-Bin Liu
See-Ying Chiou
Daniel A. Merton
Priscilla Machado
Adam P. Dicker
Levon N. Nazarian
author_facet Flemming Forsberg
Raymond J. Ro
Andrew Marshall
Ji-Bin Liu
See-Ying Chiou
Daniel A. Merton
Priscilla Machado
Adam P. Dicker
Levon N. Nazarian
author_sort Flemming Forsberg
collection DOAJ
description 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 mm 3 ). 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.
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spelling doaj-art-2ee5ff44047040b8a76ac08f99d1ede22025-01-02T23:12:07ZengSAGE PublishingMolecular Imaging1536-01212014-03-011310.2310/7290.2013.0007310.2310_7290.2013.00073The Antiangiogenic Effects of a Vascular Endothelial Growth Factor Decoy Receptor Can Be Monitored in Vivo Using Contrast-Enhanced Ultrasound ImagingFlemming ForsbergRaymond J. RoAndrew MarshallJi-Bin LiuSee-Ying ChiouDaniel A. MertonPriscilla MachadoAdam P. DickerLevon N. NazarianThe 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 mm 3 ). 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.https://doi.org/10.2310/7290.2013.00073
spellingShingle Flemming Forsberg
Raymond J. Ro
Andrew Marshall
Ji-Bin Liu
See-Ying Chiou
Daniel A. Merton
Priscilla Machado
Adam P. Dicker
Levon N. Nazarian
The Antiangiogenic Effects of a Vascular Endothelial Growth Factor Decoy Receptor Can Be Monitored in Vivo Using Contrast-Enhanced Ultrasound Imaging
Molecular Imaging
title The Antiangiogenic Effects of a Vascular Endothelial Growth Factor Decoy Receptor Can Be Monitored in Vivo Using Contrast-Enhanced Ultrasound Imaging
title_full The Antiangiogenic Effects of a Vascular Endothelial Growth Factor Decoy Receptor Can Be Monitored in Vivo Using Contrast-Enhanced Ultrasound Imaging
title_fullStr The Antiangiogenic Effects of a Vascular Endothelial Growth Factor Decoy Receptor Can Be Monitored in Vivo Using Contrast-Enhanced Ultrasound Imaging
title_full_unstemmed The Antiangiogenic Effects of a Vascular Endothelial Growth Factor Decoy Receptor Can Be Monitored in Vivo Using Contrast-Enhanced Ultrasound Imaging
title_short The Antiangiogenic Effects of a Vascular Endothelial Growth Factor Decoy Receptor Can Be Monitored in Vivo Using Contrast-Enhanced Ultrasound Imaging
title_sort antiangiogenic effects of a vascular endothelial growth factor decoy receptor can be monitored in vivo using contrast enhanced ultrasound imaging
url https://doi.org/10.2310/7290.2013.00073
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