Rat Sodium Iodide Symporter for Radioiodide Therapy of Cancer

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 l...

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Bibliographic Details
Published in:Clinical cancer research 2004-10, Vol.10 (20), p.6969-6976
Main Authors: Elena Mitrofanova, Robert Unfer, Nick Vahanian, Wayne Daniels, Erica Roberson, Tatiana Seregina, Prem Seth, Charles Link, Jr
Format: Article
Language:English
Subjects:
Adenocarcinoma - pathology
Adenoviridae
Animals
Antineoplastic agents
Biological and medical sciences
Cell Membrane
Cell Proliferation
Colorectal Neoplasms - pathology
Gene Transfer Techniques
Genetic Therapy
Genetic Vectors
Humans
Iodine Radioisotopes - pharmacokinetics
Iodine Radioisotopes - therapeutic use
Male
Medical sciences
Mice
Mice, Nude
Pharmacology. Drug treatments
Prostatic Neoplasms - pathology
Rats
Spheroids, Cellular
Symporters
Tumor Cells, Cultured
Tumors
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Summary: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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-04-0687