In Vivo magnetic resonance imaging of xenografted tumors using FTH1 reporter gene expression controlled by a tet-on switch
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Xiaoya He1,2,3,4, Jinhua Cai1,2,3,4, Hao Li1,2,3,4, Bo Liu1,2,3,4, Yong Qin1,2,3,4, Yi Zhong2,3,4, Longlun Wang1,2,3,4, Yifan Liao2,3,4
1Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China
2Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
3Key Laboratory of Pediatrics in Chongqing, Chongqing, China
4Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China
Jinhua Cai, email: email@example.com
Keywords: magnetic resonance imaging, ferritin heavy chain, tetracycline-inducible expression system, cell tracking, tumor xenograft
Received: June 14, 2016 Accepted: October 03, 2016 Published: October 08, 2016
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.
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