Noninvasive Detection of Human-Induced Pluripotent Stem Cell (hiPSC)-Derived Teratoma with an Integrin-Targeting Agent 99mTc-3PRGD2

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• 作者：Yang Li (1)
  Zhaofei Liu (2) (3)
  Chengyan Dong (2) (3)
  Peng He (2)
  Xujie Liu (1) (2)
  Zhaohui Zhu (4)
  Bing Jia (2) (3)
  Fang Li (4)
  Fan Wang (2) (3)
  
• 关键词：Induced pluripotent stem cell (iPSC) ; Teratoma ; Imaging ; Integrin αvβ3 ; 99mTc ; 3PRGD2
• 刊名：Molecular Imaging and Biology
• 出版年：2013
• 出版时间：February 2013
• 年：2013
• 卷：15
• 期：1
• 页码：58-67
• 全文大小：658KB
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• 作者单位：Yang Li (1)
  Zhaofei Liu (2) (3)
  Chengyan Dong (2) (3)
  Peng He (2)
  Xujie Liu (1) (2)
  Zhaohui Zhu (4)
  Bing Jia (2) (3)
  Fang Li (4)
  Fan Wang (2) (3)
  
  1. Stem Cell Research Center and Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
  2. Medical Isotopes Research Center, Peking University, Beijing, 100191, China
  3. Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
  4. Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, 100857, China
  

文摘

Purpose Since their discovery in 2006, induced pluripotent stem cells (iPSCs) have gained increasing interest for tissue regeneration and transplantation therapies. However, teratoma formation after iPSC transplantation is one of the most serious drawbacks that may limit their further clinical application. We investigated here whether human iPSC-derived teratomas could be detected by an integrin-targeting agent 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2). Methods Human-induced pluripotent stem cells (hiPSCs) were generated and characterized. In vitro integrin αvβ3 expression levels of hiPSC- and hiPSC-derived teratoma cells were determined by flow cytometry. 99mTc-3PRGD2 was prepared, and planar gamma imaging and biodistribution studies were carried out in teratoma-bearing severe combined immunodeficient (SCID) mice. Positron emission tomography (PET) imaging of teratomas with 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) was also performed for comparison. Integrin αvβ3 expression in teratoma tissues was determined by immunofluorescence staining. Results 99mTc-3PRGD2 showed high (2.82?±-.21 and 2.69?±-.73%ID/g at 0.5 and 1 h pi, respectively) and specific (teratoma uptake decreased from 2.69?±-.73 to 0.53?±-.26%ID/g after blocking with cold 3PRGD2) uptake in teratoma tissues, and planar gamma imaging demonstrated the feasibility of noninvasively detecting the teratoma formation with 99mTc-3PRGD2. 18F-FDG showed low teratoma uptake and thus failed to detect the teratomas. Ex vivo immunofluorescence staining validated the integrin αvβ3 expression in the vasculature during teratoma formation. Conclusion Gamma imaging with 99mTc-3PRGD2 is a promising approach for the noninvasive monitoring of tumorigenicity after hiPSCs transplantation.