title: (18)F-fluoromisonidazole PET reveals spatial and temporal heterogeneity of hypoxia in mouse models of human non-small-cell lung cancer.
abstract: OBJECTIVE
  To noninvasively observe dynamic changes in tumor hypoxia in mouse models of human non-small-cell lung cancer (NSCLC) using (18)F-fluoromisonidazole PET.
  
  
  METHODS
  Nude mice with NSCLC H460 and A549 subcutaneous xenografts were coinjected intravenously with (18)F-fluoromisonidazole and the hypoxia marker pimonidazole, and observed by serial PET scans. After sacrifice, the tumor distribution of (18)F-fluoromisonidazole and pimonidazole was compared by digital autoradiography and microscopy, respectively.
  
  
  RESULTS
  The NSCLC hypoxic microenvironment was spatially heterogeneous. Serial PET scans over 48 h revealed an apparent change in the intratumoral distribution of (18)F-fluoromisonidazole.
  
  
  CONCLUSIONS
  The tumor hypoxic microenvironment is spatially and temporally heterogeneous, and hypoxic cancer cells have a shorter life span when growing in vivo. Therefore, the concept of hypoxic resistance and hypoxia-targeting therapy of macroscopic tumors should be revisited.
authors.affiliation: Department of Nuclear Medicine, Harbin Medical University Cancer Hospital, Harbin Heilongjiang, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Cui
authors.affiliation: Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot, Inner Mongolia, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
mesh_terms: D000818:Animals; D001345:Autoradiography; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D051379:Mice; D008819:Mice, Nude; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole
keywords: 18F-fluoromisonidazole; change in hypoxia; hypoxia; non-small-cell lung cancer; tumor microenvironment