title: Molecular Imaging of Post-Src Inhibition Tumor Signatures for Guiding Dasatinib Combination Therapy.
abstract: Noninvasive, real-time, quantitative measurement of key biomarkers associated with cancer therapeutic interventions could provide a better understanding of cancer biology. We investigated in this study whether incorporating multiple molecular imaging approaches could be used to guide dasatinib anti-Src therapy and aid in the rational design of a combination therapy regimen.
  
  
  METHODS
  Bioluminescence imaging, (18)F-FDG PET, integrin αvβ3-targeted SPECT/CT, and vascular endothelial growth factor-targeted near-infrared fluorescence imaging were performed before and after dasatinib treatment in a tumor mouse model.
  
  
  RESULTS
  There was no significant difference in the bioluminescence imaging signal or (18)F-FDG tumor uptake in dasatinib-treated tumors compared with the control tumors. However, the uptake of (99m)T-3PRGD2 (integrin αvβ3-specific) and DyLight755-ranibizumab (vascular endothelial growth factor-specific) in the dasatinib-treated tumors was significantly lower than that in the control tumors. In vitro studies confirmed the antiangiogenic effects of dasatinib but indicated a lack of cytotoxicity. Dasatinib plus cytotoxic docetaxel elicited marked synergistic tumor growth inhibition in vivo.
  
  
  CONCLUSIONS
  Visualization of post-Src inhibition tumor signatures through multiple imaging approaches facilitates sensitive and quantitative measurement of cancer biomarkers in vivo, thus aiding in the rational design of dasatinib combination therapy.
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Liquan
authors.initials: L
authors.lastname: Gao
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Xianlei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Gao
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Chenran
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.affiliation: Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China; and.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China liuzf@bjmu.edu.cn.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069439:Dasatinib / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D016391:Genes, src / Q000187:drug effects*; D039302:Integrin alphaVbeta3 / Q000187:drug effects; D049449:Luminescence; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging; D009369:Neoplasms / Q000188:drug therapy*; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D000069579:Ranibizumab / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D039302:Integrin alphaVbeta3; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18; D000069439:Dasatinib; D000069579:Ranibizumab
keywords: Src family of kinases; angiogenesis; dasatinib; image-guided therapy; tumor response