title: Theranostic studies of human sodium iodide symporter imaging and therapy using 188Re: a human glioma study in mice.
abstract: OBJECTIVE
  To investigate the role of 188Re in human sodium iodide symporter (hNIS) theranostic gene-mediated human glioma imaging and therapy in model mice.
  
  
  METHODS
  The human glioma cell line U87 was transfected with recombinant lentivirus encoding the hNIS gene under the control of cytomegalovirus promoter (U87-hNIS). The uptake and efflux of 188Re were determined after incubating the cells with 188Re. 188Re uptake experiments in the presence of various concentrations of sodium perchlorate were carried out. In vitro cell killing tests with 188Re were performed. U87-hNIS mediated 188Re distribution, imaging and therapy in nude mice were also tested.
  
  
  RESULTS
  U87-hNIS cell line was successfully established. The uptake of 188Re in U87-hNIS cells increased up to 26-fold compared to control cells, but was released rapidly with a half-life of approximately 4 minutes. Sodium perchlorate reduced hNIS-mediated 188Re uptake to levels of control cell lines. U87-hNIS cells were selectively killed following exposure to 188Re, with a survival of 21.4%, while control cells had a survival of 92.1%. Unlike in vitro studies, U87-hNIS tumor showed a markedly increased 188Re retention even 48 hours after 188Re injection. In the therapy study, there was a significant difference in tumor size between U87-hNIS mice (317±67 mm3) and control mice (861±153 mm3) treated with 188Re for 4 weeks (P<0.01).
  
  
  CONCLUSIONS
  The results indicate that inserting the hNIS gene into U87 cells is sufficient to induce specific 188Re uptake, which has a cell killing effect both in vitro and in vivo. Moreover, our study, based on the function of hNIS as a theranostic gene allowing noninvasive imaging of hNIS expression by 188Re scintigraphy, provides detailed characterization of in vivo vector biodistribution and level, localization, essential prerequisites for precise planning and monitoring of clinical gene therapy that aims to individualize gene therapy concept.
authors.affiliation: Department of Nuclear Medicine, Rui Jin Hospital, School of medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Nuclear Medicine, Rui Jin Hospital, School of medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Rui Jin Hospital, School of medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Nuclear Medicine, Xin Hua Hospital, School of medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Nuclear Medicine, Xin Hua Hospital, School of medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Nuclear Medicine, Rui Jin Hospital, School of medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Nuclear Medicine, Rui Jin Hospital, School of medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Nuclear Medicine, Rui Jin Hospital, School of medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy; D003952:Diagnostic Imaging; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D011877:Radionuclide Imaging; D012211:Rhenium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
chemical_list: D012211:Rhenium; D027981:Symporters; D000099209:Sodium-Iodide Symporters