title: Radioiodide treatment after sodium iodide symporter gene transfer is a highly effective therapy in neuroendocrine tumor cells.
abstract: This study evaluates the possibility of treating Bon1 and QGP pancreatic neuroendocrine tumor cells with radioactive iodide ((131)I) after stable transfection with the thyroid sodium iodide symporter (NIS). NIS expression was driven either by the strong viral cytomegalovirus promoter or by the tissue-specific chromogranin A promoter. Using either approach, NIS expression was confirmed by reverse transcription-PCR and Western blotting. Uptake of radioactive iodide was increased approximately 20-fold by chromogranin A promoter-driven NIS expression and approximately 50-fold by cytomegalovirus promoter-driven NIS expression. Maximal uptake was reached within 15 min in QGP cells and 30 min in Bon1 cells. Effective half-life was 5 min in QGP and 30 min in Bon1 cells. No evidence of organification was detected by high-performance liquid chromatography and gel filtration chromatography. (131)I was a highly effective treatment in NIS-expressing QGP and Bon1 cells, reducing clone formation by 99.83 and 98.75%, respectively, in the in vitro clonogenic assay. In contrast, clone formation was not reduced in QGP and Bon1 cells without NIS expression after incubation with the same activity concentration of (131)I as compared with mock treated cells. Absorbed doses to QGP and Bon1 cells are up to 150 and 30 Gy, respectively. In addition, a direct cytotoxic effect of radioiodide was demonstrated in NIS-expressing Bon1 cells after (131)I incubation. In conclusion, radioiodide treatment after NIS gene transfer appears to be a promising novel approach in the therapy of neuroendocrine tumors if its highly encouraging in vitro effectiveness can be transferred to the in vivo situation.
authors.affiliation: Departments of Nuclear Medicine, Philipps University Marburg, 35043 Marburg, Germany. schipper@mailer.uni-marburg.de
authors.forename: Meike L
authors.initials: ML
authors.lastname: Schipper
authors.forename: Alexander
authors.initials: A
authors.lastname: Weber
authors.forename: Martin
authors.initials: M
authors.lastname: Béhé
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Göke
authors.forename: Werner
authors.initials: W
authors.lastname: Joba
authors.forename: Harald
authors.initials: H
authors.lastname: Schmidt
authors.forename: Till
authors.initials: T
authors.lastname: Bert
authors.forename: Babette
authors.initials: B
authors.lastname: Simon
authors.forename: Rudolf
authors.initials: R
authors.lastname: Arnold
authors.forename: Armin E
authors.initials: AE
authors.lastname: Heufelder
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Behr
mesh_terms: D002276:Carcinoid Tumor / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007454:Iodides / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D027981:Symporters / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters
chemical_list: D007454:Iodides; D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters