title: In Vivo magnetic resonance imaging of xenografted tumors using FTH1 reporter gene expression controlled by a tet-on switch.
abstract: As a promising magnetic resonance imaging (MRI) reporter, ferritin has been used to track cells in vivo; however, its continuous overexpression can be cytotoxic, which restricts its application. In this study, we aimed to develop a switch to turn this genetic reporter "on" or "off" while monitoring cell grafts via MRI. To accomplish this, we genetically modified the ferritin heavy chain (FTH1) with a Tet-On switch and assessed the expression of FTH1 in transduced neuroblastoma cells (SK-N-SH) in vitro and in xenografted tumors in vivo. We found that FTH1 expression induced by doxycycline (Dox) in SK-N-SH-FTH1 cells depended on treatment dose and duration. We successfully detected T2-weighted MRI contrast in cell grafts after switching "on" the reporter gene using Dox, and this contrast disappeared when we switched it "off". The genetic reporter FTH1 can thus be switched "on" or "off" throughout longitudinal monitoring of cell grafts, limiting expression to when MRI contrast is needed. The controllable imaging system we have developed minimizes risks from constitutive reporter gene overexpression and facilitates tumor cell monitoring in vitro and in vivo.
authors.affiliation: Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Xiaoya
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Longlun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Liao
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology*; D005293:Ferritins / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter; D064593:Heterografts; D006801:Humans; D007501:Iron / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D014408:Biomarkers, Tumor; D005293:Ferritins; D007501:Iron; C454461:FTH1 protein, human; D010088:Oxidoreductases; D004318:Doxycycline
keywords: cell tracking; ferritin heavy chain; magnetic resonance imaging; tetracycline-inducible expression system; tumor xenograft