title: Mapping in vivo tumor oxygenation within viable tumor by 19F-MRI and multispectral analysis.
abstract: Quantifying oxygenation in viable tumor remains a major obstacle toward a better understanding of the tumor micro-environment and improving treatment strategies. Current techniques are often complicated by tumor heterogeneity. Herein, a novel in vivo approach that combines (19)F magnetic resonance imaging ((19)F-MRI) R 1 mapping with diffusion-based 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 (19)F-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.
authors: Department of Biomedical Imaging, Genentech Inc, South San Francisco, CA.
authors: Yunzhou
authors: Y
authors: Shi
authors: Jason
authors: J
authors: Oeh
authors: Jeffrey
authors: J
authors: Eastham-Anderson
authors: Sharon
authors: S
authors: Yee
authors: David
authors: D
authors: Finkle
authors: Franklin V
authors: FV
authors: Peale
authors: Jed
authors: J
authors: Ross
authors: Maj
authors: M
authors: Hedehus
authors: Nicholas
authors: N
authors: van Bruggen
authors: Rayna
authors: R
authors: Venook
authors: Sarajane
authors: S
authors: Ross
authors: Deepak
authors: D
authors: Sampath
authors: Richard A D
authors: RA
authors: Carano
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D064593:Heterografts; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D010100:Oxygen / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D010100:Oxygen; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human