title: Rat sodium iodide symporter for radioiodide therapy of cancer.
abstract: Design and development of new approaches for targeted radiotherapy of cancer and improvement of therapeutic index by more local radiation therapy are very important issues. Adenovirus-mediated delivery of the sodium iodide symporter (NIS) gene to cancer cells is a powerful technique to concentrate lethal radiation in tumor cells and eradicate tumors with increased therapeutic index. A replication-defective adenoviral vector expressing the rat NIS gene (Ad-rNIS) was used for in vitro gene delivery and into human prostate cancer xenografts to study antitumor effect. Robust function of the rat symporter was detected in DU145, T47D, and HCT-15 human cancer cell lines transduced with Ad-rNIS. All three cancer cell lines successfully transferred functionally active rat symporter to the plasma membrane, resulting in very high levels of iodine-125 accumulation. Three-dimensional multicellular tumor spheroids derived from DU145 human prostate cancer cells were transduced with Ad-rNIS and incubated with (131)I for 24 hours. After treatment, spheroids rapidly decreased in size and disappeared within 10 days. In vivo data revealed an inhibition of tumor growth in athymic nude mice after intratumoral Ad-rNIS injection followed by (131)I administration. Eighty-eight percent of experimental mice survived >30 days, whereas control groups had only 18% survival >30 days. This is the first report that demonstrates the rat NIS gene can effectively induce growth arrest of human tumor xenografts after in vivo adenoviral gene delivery and (131)I administration. The data confirm our hypothesis that the rat NIS gene is an attractive suicide gene candidate for cancer treatment.
authors.affiliation: Iowa Cancer Research Foundation, Des Moines, Iowa, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Mitrofanova
authors.forename: Robert
authors.initials: R
authors.lastname: Unfer
authors.forename: Nick
authors.initials: N
authors.lastname: Vahanian
authors.forename: Wayne
authors.initials: W
authors.lastname: Daniels
authors.forename: Erica
authors.initials: E
authors.lastname: Roberson
authors.forename: Tatiana
authors.initials: T
authors.lastname: Seregina
authors.forename: Prem
authors.initials: P
authors.lastname: Seth
authors.forename: Charles
authors.initials: C
authors.lastname: Link
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000256:Adenoviridae; D000818:Animals; D002462:Cell Membrane; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000473:pathology; D051381:Rats; D018874:Spheroids, Cellular; D027981:Symporters; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters