| Title | Noninvasive Detection of Human-Induced Pluripotent Stem Cell (hiPSC)-Derived Teratoma with an Integrin-Targeting Agent Tc-99m-3PRGD2 |
| Authors | Li, Yang Liu, Zhaofei Dong, Chengyan He, Peng Liu, Xujie Zhu, Zhaohui Jia, Bing Li, Fang Wang, Fan |
| Affiliation | Peking Univ, Sch Basic Med Sci, Stem Cell Res Ctr, Beijing 100191, Peoples R China. Peking Univ, Sch Basic Med Sci, Dept Cell Biol, Beijing 100191, Peoples R China. Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China. Peking Univ, Sch Basic Med Sci, Dept Radiat Med, Beijing 100191, Peoples R China. Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing 100857, Peoples R China. |
| Keywords | Induced pluripotent stem cell (iPSC) Teratoma Imaging Integrin alpha(v)beta(3) Tc-99m-3PRGD2 POSITRON-EMISSION-TOMOGRAPHY TUMOR-CELLS ANGIOGENESIS THERAPY DISEASE CANCER PET |
| Issue Date | 2013 |
| Publisher | molecular imaging and biology |
| Citation | MOLECULAR IMAGING AND BIOLOGY.2013,15,(1),58-67. |
| Abstract | 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 Tc-99m-PEG(4)-E[PEG(4)-c(RGDfK)](2) (Tc-99m-3PRGD2). Human-induced pluripotent stem cells (hiPSCs) were generated and characterized. In vitro integrin alpha(v)beta(3) expression levels of hiPSC- and hiPSC-derived teratoma cells were determined by flow cytometry. Tc-99m-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-[F-18]fluoro-d-glucose (F-18-FDG) was also performed for comparison. Integrin alpha(v)beta(3) expression in teratoma tissues was determined by immunofluorescence staining. Tc-99m-3PRGD2 showed high (2.82 +/- 0.21 and 2.69 +/- 0.73%ID/g at 0.5 and 1 h pi, respectively) and specific (teratoma uptake decreased from 2.69 +/- 0.73 to 0.53 +/- 0.26%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 Tc-99m-3PRGD2. F-18-FDG showed low teratoma uptake and thus failed to detect the teratomas. Ex vivo immunofluorescence staining validated the integrin alpha(v)beta(3) expression in the vasculature during teratoma formation. Gamma imaging with Tc-99m-3PRGD2 is a promising approach for the noninvasive monitoring of tumorigenicity after hiPSCs transplantation. |
| URI | http://hdl.handle.net/20.500.11897/191244 |
| ISSN | 1536-1632 |
| DOI | 10.1007/s11307-012-0571-1 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 基础医学院 |
