Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis

Quantifying oxygenation in viable tumor remains a major obstacle toward a better understanding of the tumor microenvironment and improving treatment strategies. Current techniques are often complicated by tumor heterogeneity. Herein, a novel in vivo approach that combines 19F magnetic resonance imag...

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Main Authors: Yunzhou Shi, Jason Oeh, Jeffrey Eastham-Anderson, Sharon Yee, David Finkle, Franklin V. Peale, Jr, Jed Ross, Maj Hedehus, Nicholas van Bruggen, Rayna Venook, Sarajane Ross, Deepak Sampath, Richard A.D. Carano
Format: Article
Language:English
Published: Elsevier 2013-11-01
Series:Neoplasia: An International Journal for Oncology Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1476558613800851
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author Yunzhou Shi
Jason Oeh
Jeffrey Eastham-Anderson
Sharon Yee
David Finkle
Franklin V. Peale, Jr
Jed Ross
Maj Hedehus
Nicholas van Bruggen
Rayna Venook
Sarajane Ross
Deepak Sampath
Richard A.D. Carano
author_facet Yunzhou Shi
Jason Oeh
Jeffrey Eastham-Anderson
Sharon Yee
David Finkle
Franklin V. Peale, Jr
Jed Ross
Maj Hedehus
Nicholas van Bruggen
Rayna Venook
Sarajane Ross
Deepak Sampath
Richard A.D. Carano
author_sort Yunzhou Shi
collection DOAJ
description Quantifying oxygenation in viable tumor remains a major obstacle toward a better understanding of the tumor microenvironment and improving treatment strategies. Current techniques are often complicated by tumor heterogeneity. Herein, a novel in vivo approach that combines 19F magnetic resonance imaging (19F-MRI)R1 mapping with diffusionbased multispectral (MS) analysis is introduced. This approach restricts the partial pressure of oxygen (pO2) measurements to viable tumor, the tissue of therapeutic interest. The technique exhibited sufficient sensitivity to detect a breathing gas challenge in a xenograft tumor model, and the hypoxic region measured by MS 19F-MRI was strongly correlated with histologic estimates of hypoxia. This approach was then applied to address the effects of antivascular agents on tumor oxygenation, which is a research question that is still under debate. The technique was used to monitor longitudinal pO2 changes in response to an antibody to vascular endothelial growth factor (B20.4.1.1) and a selective dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor (GDC-0980). GDC-0980 reduced viable tumor pO2 during a 3-day treatment period, and a significant reduction was also produced by B20.4.1.1. Overall, this method provides an unprecedented view of viable tumor pO2 and contributes to a greater understanding of the effects of antivascular therapies on the tumor's microenvironment.
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spelling doaj.art-7914fc373e614f65bd3e6d578cf2491d2022-12-22T03:07:39ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022013-11-0115111241125010.1593/neo.131468Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral AnalysisYunzhou Shi0Jason Oeh1Jeffrey Eastham-Anderson2Sharon Yee3David Finkle4Franklin V. Peale, Jr5Jed Ross6Maj Hedehus7Nicholas van Bruggen8Rayna Venook9Sarajane Ross10Deepak Sampath11Richard A.D. Carano12Department of Biomedical Imaging, Genentech Inc, South San Francisco, CADepartment of Translational Oncology, 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 Pathology, Genentech Inc, South San Francisco, CADepartment of Biomedical Imaging, Genentech Inc, South San Francisco, CADepartment of Biomedical Imaging, Genentech Inc, South San Francisco, CADepartment 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 Translational Oncology, Genentech Inc, South San Francisco, CADepartment of Biomedical Imaging, Genentech Inc, South San Francisco, CAQuantifying oxygenation in viable tumor remains a major obstacle toward a better understanding of the tumor microenvironment and improving treatment strategies. Current techniques are often complicated by tumor heterogeneity. Herein, a novel in vivo approach that combines 19F magnetic resonance imaging (19F-MRI)R1 mapping with diffusionbased multispectral (MS) analysis is introduced. This approach restricts the partial pressure of oxygen (pO2) measurements to viable tumor, the tissue of therapeutic interest. The technique exhibited sufficient sensitivity to detect a breathing gas challenge in a xenograft tumor model, and the hypoxic region measured by MS 19F-MRI was strongly correlated with histologic estimates of hypoxia. This approach was then applied to address the effects of antivascular agents on tumor oxygenation, which is a research question that is still under debate. The technique was used to monitor longitudinal pO2 changes in response to an antibody to vascular endothelial growth factor (B20.4.1.1) and a selective dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor (GDC-0980). GDC-0980 reduced viable tumor pO2 during a 3-day treatment period, and a significant reduction was also produced by B20.4.1.1. Overall, this method provides an unprecedented view of viable tumor pO2 and contributes to a greater understanding of the effects of antivascular therapies on the tumor's microenvironment.http://www.sciencedirect.com/science/article/pii/S1476558613800851
spellingShingle Yunzhou Shi
Jason Oeh
Jeffrey Eastham-Anderson
Sharon Yee
David Finkle
Franklin V. Peale, Jr
Jed Ross
Maj Hedehus
Nicholas van Bruggen
Rayna Venook
Sarajane Ross
Deepak Sampath
Richard A.D. Carano
Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis
Neoplasia: An International Journal for Oncology Research
title Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis
title_full Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis
title_fullStr Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis
title_full_unstemmed Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis
title_short Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis
title_sort mapping in vivo tumor oxygenation within viable tumor by 19f mri and multispectral analysis
url http://www.sciencedirect.com/science/article/pii/S1476558613800851
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