title: MR molecular imaging of tumours using ferritin heavy chain reporter gene expression mediated by the hTERT promoter.
abstract: OBJECTIVE
  Using the human telomerase reverse transcriptase (hTERT) promoter and the modified ferritin heavy chain (Fth) reporter gene, reporter gene expression for MRI was examined in telomerase positive and negative tumour cells and xenografts.
  
  
  METHODS
  Activity of the reporter gene expression vector Lenti-hTERT-Fth1-3FLAG-Puro was compared to constitutive CMV-driven expression and to the untransfected parental control in five tumour cell lines: A549, SKOV3, 293T, U2OS and HPDLF. In vitro, transfected cells were evaluated for FLAG-tagged protein expression, iron accumulation and transverse relaxation. In vivo, tumours transduced by lentiviral vector injection were imaged using T2*WI. Changes in tumour signal intensity were validated by histology.
  
  
  RESULTS
  Only telomerase positive tumour cells expressed FLAG-tagged Fth and displayed an increase in R2* above the parental control, with a corresponding change in T2*WI. In addition, only telomerase positive tumours, transduced by injection of the reporter gene expression construct, exhibited a change in signal intensity on T2*WI. Tumour histology verified the expression of FLAG-tagged Fth and iron accumulation in telomerase positive tissue.
  
  
  CONCLUSIONS
  Reporter gene expression for MRI, using the Fth reporter and the hTERT promoter, may be a useful strategy for the non-invasive diagnosis of many types of cancer.
  
  
  CONCLUSIONS
  • Modified heavy chain of ferritin can serve as an MR reporter gene • hTERT promoter can direct the expression of reporter gene in cancer cells • MR reporter imaging mediated by hTERT promoter can be used for cancer diagnosis.
authors.affiliation: Department of Radiology, XinQiao Hospital, Third Military Medical University, ChongQing, 400037, People's Republic of China.|Department of Radiology, The First Affiliated Hospital of ChengDu Medical College, ChengDu, 610500, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiology, XinQiao Hospital, Third Military Medical University, ChongQing, 400037, People's Republic of China.
authors.forename: Ming-Fu
authors.initials: MF
authors.lastname: Gong
authors.affiliation: Department of Radiology, XinQiao Hospital, Third Military Medical University, ChongQing, 400037, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Radiology, XinQiao Hospital, Third Military Medical University, ChongQing, 400037, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Radiology, XinQiao Hospital, Third Military Medical University, ChongQing, 400037, People's Republic of China.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Wang
authors.affiliation: Department of Radiology, XinQiao Hospital, Third Military Medical University, ChongQing, 400037, People's Republic of China.
authors.forename: Tong-Sheng
authors.initials: TS
authors.lastname: Su
authors.affiliation: Department of Radiology, XinQiao Hospital, Third Military Medical University, ChongQing, 400037, People's Republic of China. cqzdwl@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Radiology, XinQiao Hospital, Third Military Medical University, ChongQing, 400037, People's Republic of China. hszhangd@163.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001052:Apoferritins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis*; D011401:Promoter Regions, Genetic / Q000235:genetics; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D001052:Apoferritins; C509186:TERT protein, human; D019098:Telomerase
keywords: Ferritin heavy chain; Magnetic resonance imaging; Neoplasm; Reporter gene expression; hTERT