title: VEGFR2-Targeted Three-Dimensional Ultrasound Imaging Can Predict Responses to Antiangiogenic Therapy in Preclinical Models of Colon Cancer.
abstract: Three-dimensional (3D) imaging capabilities to assess responses to anticancer therapies are needed to minimize sampling errors common to two-dimensional approaches as a result of spatial heterogeneity in tumors. Recently, the feasibility and reproducibility of 3D ultrasound molecular imaging (3D USMI) using contrast agents, which target molecular markers, have greatly improved, due to the development of clinical 3D matrix array transducers. Here we report preclinical proof-of-concept studies showing that 3D USMI of VEGFR2/KDR expression accurately gauges longitudinal treatment responses to antiangiogenesis therapy in responding versus nonresponding mouse models of colon cancer. Tumors in these models exhibited differential patterns of VEGFR2-targeted 3D USMI signals during the course of antiangiogenic treatment with bevacizumab. In responding tumors, the VEGFR2 signal decreased as soon as 24 hours after therapy was started, whereas in nonresponding tumors there was no change in signal at any time point. The early decrease in VEGFR2 signal was highly predictive of treatment outcome at the end of therapy. Our results offer preclinical proof that 3D USMI can predict responses to antiangiogenic therapy, warranting further investigation of its clinical translatability to predicting treatment outcomes in patients. Cancer Res; 76(14); 4081-9. ©2016 AACR.
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California. Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California.
authors.forename: Huaijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California.
authors.forename: Amelie M
authors.initials: AM
authors.lastname: Lutz
authors.affiliation: Department of Health, Research & Policy, Stanford University, Stanford, California.
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Dimitre
authors.initials: D
authors.lastname: Hristov
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California. willmann@stanford.edu.
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Willmann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D003287:Contrast Media; D006801:Humans; D021621:Imaging, Three-Dimensional; D051379:Mice; D045423:Microbubbles; D014463:Ultrasonography; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis*
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2