title: Phosphorescence monitoring of hypoxic microenvironment in solid-tumors to evaluate chemotherapeutic effects using the hypoxia-sensitive iridium (III) coordination compound.
abstract: To utilize phosphorescence to monitor hypoxic microenvironment in solid-tumors and investigate cancer chemotherapeutic effects in vivo.
  
  
  
  A hypoxia-sensitive probe named BTP was used to monitor hypoxic microenvironment in solid-tumors. The low-dose metronomic treatment with cisplatin was used in anti-angiogenetic chemotherapeutic programs. The phosphorescence properties of BTP were detected by a spectrofluorometer. BTP cytotoxicity utilized cell necrosis and apoptosis, which were evaluated by trypan blue dye exclusion and Hoechst33342 plus propidium iodide assays. Tumor-bearing mouse models of colon adenocarcinoma were used for tumor imaging in vivo. Monitoring of the hypoxic microenvironment in tumors was performed with a Maestro 2 fluorescence imaging system. Tumor tissues in each group were harvested regularly and treated with pathological hematoxylin and eosin and immunohistochemical staining to confirm imaging results.
  
  
  
  BTP did not feature obvious cytotoxicity for cells, and tumor growth in low-dose metronomic cisplatin treated mice was significantly inhibited by chemotherapy. Hypoxic levels significantly increased due to cisplatin, as proven by the expression level of related proteins. Phosphorescence intensity in the tumors of mice in the cisplatin group was stronger and showed higher contrast than that in tumors of saline treated mice.
  
  
  
  We develop a useful phosphorescence method to evaluate the chemotherapeutic effects of cisplatin. The proposed method shows potential as a phosphorescence imaging approach for evaluating chemotherapeutic effects in vivo, especially anti-angiogenesis.
authors.affiliation: The Key Laboratory of Biomedical Information Engineering, Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Radiology Department, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shang
authors.affiliation: The Key Laboratory of Biomedical Information Engineering, Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Ma
authors.affiliation: Radiology Department, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Radiology Department, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Deng
authors.affiliation: Radiology Department, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Youmin
authors.initials: Y
authors.lastname: Guo
authors.affiliation: School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Bai
authors.affiliation: Radiology Department, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, P. R. China; Molecular Imaging Laboratory, Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Biomedical Information Engineering, Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Daocheng
authors.initials: D
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology*; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D007495:Iridium / Q000737:chemistry*; D049408:Luminescent Agents / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D008163:Luminescent Measurements; D051379:Mice; D061848:Optical Imaging; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D049408:Luminescent Agents; D009942:Organometallic Compounds; C000604869:bis(2,(2'-benzothienyl)-pyridinato-N,C3')(acetylacetonate)Ir(III); D007495:Iridium; D002945:Cisplatin