Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F–MRI and Multispectral Analysis
The effect of anti-angiogenic agents on tumor oxygenation has been in question for a number of years, where both increases and decreases in tumor pO2 have been observed. This dichotomy in results may be explained by the role of vessel normalization in the response of tumors to anti-angiogenic therap...
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Format: | Article |
Language: | English |
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Elsevier
2017-11-01
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Series: | Neoplasia: An International Journal for Oncology Research |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558617303251 |
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author | Yunzhou Shi Jason Oeh Anna Hitz Maj Hedehus Jeffrey Eastham-Anderson Franklin V. Peale, Jr. Patricia Hamilton Thomas O'Brien Deepak Sampath Richard A.D. Carano |
author_facet | Yunzhou Shi Jason Oeh Anna Hitz Maj Hedehus Jeffrey Eastham-Anderson Franklin V. Peale, Jr. Patricia Hamilton Thomas O'Brien Deepak Sampath Richard A.D. Carano |
author_sort | Yunzhou Shi |
collection | DOAJ |
description | The effect of anti-angiogenic agents on tumor oxygenation has been in question for a number of years, where both increases and decreases in tumor pO2 have been observed. This dichotomy in results may be explained by the role of vessel normalization in the response of tumors to anti-angiogenic therapy, where anti-angiogenic therapies may initially improve both the structure and the function of tumor vessels, but more sustained or potent anti-angiogenic treatments will produce an anti-vascular response, producing a more hypoxic environment. The first goal of this study was to employ multispectral (MS) 19F–MRI to noninvasively quantify viable tumor pO2 and evaluate the ability of a high dose of an antibody to vascular endothelial growth factor (VEGF) to produce a strong and prolonged anti-vascular response that results in significant tumor hypoxia. The second goal of this study was to target the anti-VEGF induced hypoxic tumor micro-environment with an agent, tirapazamine (TPZ), which has been designed to target hypoxic regions of tumors. These goals have been successfully met, where an antibody that blocks both murine and human VEGF-A (B20.4.1.1) was found by MS 19F–MRI to produce a strong anti-vascular response and reduce viable tumor pO2 in an HM-7 xenograft model. TPZ was then employed to target the anti-VEGF-induced hypoxic region. The combination of anti-VEGF and TPZ strongly suppressed HM-7 tumor growth and was superior to control and both monotherapies. This study provides evidence that clinical trials combining anti-vascular agents with hypoxia-activated prodrugs should be considered to improved efficacy in cancer patients. |
first_indexed | 2024-12-23T20:41:59Z |
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id | doaj.art-1b96baaaac2f4413aedd350f7287303d |
institution | Directory Open Access Journal |
issn | 1476-5586 1522-8002 |
language | English |
last_indexed | 2024-12-23T20:41:59Z |
publishDate | 2017-11-01 |
publisher | Elsevier |
record_format | Article |
series | Neoplasia: An International Journal for Oncology Research |
spelling | doaj.art-1b96baaaac2f4413aedd350f7287303d2022-12-21T17:31:53ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022017-11-01191195095910.1016/j.neo.2017.07.010Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F–MRI and Multispectral AnalysisYunzhou Shi0Jason Oeh1Anna Hitz2Maj Hedehus3Jeffrey Eastham-Anderson4Franklin V. Peale, Jr.5Patricia Hamilton6Thomas O'Brien7Deepak Sampath8Richard A.D. Carano9Department of Biomedical Imaging, Genentech Inc., South San Francisco, CADepartment of Translational Oncology, Genentech Inc., South San Francisco, CADepartment of Translational Oncology, Genentech Inc., South San Francisco, CADepartment of Biomedical Imaging, Genentech Inc., South San Francisco, CADepartment of Pathology, Genentech Inc., South San Francisco, CADepartment of Pathology, Genentech Inc., South San Francisco, CADepartment of Translational Oncology, Genentech Inc., South San Francisco, CADepartment of Translational Oncology, Genentech Inc., South San Francisco, CADepartment of Translational Oncology, Genentech Inc., South San Francisco, CADepartment of Biomedical Imaging, Genentech Inc., South San Francisco, CAThe effect of anti-angiogenic agents on tumor oxygenation has been in question for a number of years, where both increases and decreases in tumor pO2 have been observed. This dichotomy in results may be explained by the role of vessel normalization in the response of tumors to anti-angiogenic therapy, where anti-angiogenic therapies may initially improve both the structure and the function of tumor vessels, but more sustained or potent anti-angiogenic treatments will produce an anti-vascular response, producing a more hypoxic environment. The first goal of this study was to employ multispectral (MS) 19F–MRI to noninvasively quantify viable tumor pO2 and evaluate the ability of a high dose of an antibody to vascular endothelial growth factor (VEGF) to produce a strong and prolonged anti-vascular response that results in significant tumor hypoxia. The second goal of this study was to target the anti-VEGF induced hypoxic tumor micro-environment with an agent, tirapazamine (TPZ), which has been designed to target hypoxic regions of tumors. These goals have been successfully met, where an antibody that blocks both murine and human VEGF-A (B20.4.1.1) was found by MS 19F–MRI to produce a strong anti-vascular response and reduce viable tumor pO2 in an HM-7 xenograft model. TPZ was then employed to target the anti-VEGF-induced hypoxic region. The combination of anti-VEGF and TPZ strongly suppressed HM-7 tumor growth and was superior to control and both monotherapies. This study provides evidence that clinical trials combining anti-vascular agents with hypoxia-activated prodrugs should be considered to improved efficacy in cancer patients.http://www.sciencedirect.com/science/article/pii/S1476558617303251 |
spellingShingle | Yunzhou Shi Jason Oeh Anna Hitz Maj Hedehus Jeffrey Eastham-Anderson Franklin V. Peale, Jr. Patricia Hamilton Thomas O'Brien Deepak Sampath Richard A.D. Carano Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F–MRI and Multispectral Analysis Neoplasia: An International Journal for Oncology Research |
title | Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F–MRI and Multispectral Analysis |
title_full | Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F–MRI and Multispectral Analysis |
title_fullStr | Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F–MRI and Multispectral Analysis |
title_full_unstemmed | Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F–MRI and Multispectral Analysis |
title_short | Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F–MRI and Multispectral Analysis |
title_sort | monitoring and targeting anti vegf induced hypoxia within the viable tumor by 19f mri and multispectral analysis |
url | http://www.sciencedirect.com/science/article/pii/S1476558617303251 |
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