title: Ferritin heavy chain as a molecular imaging reporter gene in glioma xenografts.
abstract: OBJECTIVE
  The development of glioma therapy in clinical practice (e.g., gene therapy) calls for efficiently visualizing and tracking glioma cells in vivo. Human ferritin heavy chain is a novel gene reporter in magnetic resonance imaging. This study proposes hFTH as a reporter gene for MR molecular imaging in glioma xenografts.
  
  
  METHODS
  Rat C6 glioma cells were infected by packaged lentivirus carrying hFTH and EGFP genes and obtained by fluorescence-activated cell sorting. The iron-loaded ability was analyzed by the total iron reagent kit. Glioma nude mouse models were established subcutaneously and intracranially. Then, in vivo tumor bioluminescence was performed via the IVIS spectrum imaging system. The MR imaging analysis was analyzed on a 7T animal MRI scanner. Finally, the expression of hFTH was analyzed by western blotting and histological analysis.
  
  
  RESULTS
  Stable glioma cells carrying hFTH and EGFP reporter genes were successfully obtained. The intracellular iron concentration was increased without impairing the cell proliferation rate. Glioma cells overexpressing hFTH showed significantly decreased signal intensity on T2-weighted MRI both in vitro and in vivo. EGFP fluorescent imaging could also be detected in the subcutaneous and intracranial glioma xenografts. Moreover, the expression of the transferritin receptor was significantly increased in glioma cells carrying the hFTH reporter gene.
  
  
  CONCLUSIONS
  Our study illustrated that hFTH generated cellular MR imaging contrast efficiently in glioma via regulating the expression of transferritin receptor. This might be a useful reporter gene in cell tracking and MR molecular imaging for glioma diagnosis, gene therapy and tumor metastasis.
authors.affiliation: Brain Tumor Research Center, Beijing Laboratory of Biomedical Materials, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Sen
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Brain Tumor Research Center, Beijing Laboratory of Biomedical Materials, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Mi
authors.affiliation: Radiology Department, Dongzhimen Hospital Beijing University of Chinese Medicine, No. 5 Hai Yun Cang, Dong Cheng District, Beijing, 100700, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Brain Tumor Research Center, Beijing Laboratory of Biomedical Materials, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Guishan
authors.initials: G
authors.lastname: Jin
authors.affiliation: Brain Tumor Research Center, Beijing Laboratory of Biomedical Materials, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Junwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Brain Tumor Research Center, Beijing Laboratory of Biomedical Materials, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Radiology Department, Dongzhimen Hospital Beijing University of Chinese Medicine, No. 5 Hai Yun Cang, Dong Cheng District, Beijing, 100700, People's Republic of China. guangchen999@sina.com.
authors.forename: Zhengguang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Brain Tumor Research Center, Beijing Laboratory of Biomedical Materials, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing, 100050, People's Republic of China. liufushengs@hotmail.com.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000032:analysis* / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D051381:Rats
chemical_list: D001052:Apoferritins
keywords: Glioma; Human ferritin heavy chain; Molecular imaging; Reporter gene