Journal
GENE THERAPY
Volume 9, Issue 17, Pages 1139-1145Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3301787
Keywords
sodium/iodide symporter; radionuclide imaging; gene therapy; recombinant retrovirus; thyroid; brain neoplasm
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Radioactive iodide uptake (RAW) in thyroid follicular epithelial cells, mediated by the sodium iodide symporter (NIS), is the first rate-limiting step in iodide accumulation which provides a mechanism for effective radioiodide treatment for patients with thyroid cancer. We hypothesize that NIS gene transfer to non-thyroid tumor cells will enhance intracellular radioiodide accumulation and result in better tumor control. Here, we performed non-invasive tumor imaging and I-131 therapy studies using rats bearing intracerebral F98 gliomas that have been retrovirally transduced with human NIS. Our results show that (1) NIS is expressed in the intracerebral F98/NIS gliomas; (2) F98/NIS gliomas can be imaged by (99)mTcO(4), (whose uptake is also mediated by NIS) and I-123 scintigraphy, (3) significant amounts of radioiodide were retained in the tumors at 24 h after I-123 injection; (4) RAW and NIS expression in the thyroid gland can be reduced by feeding a thyroxine-supplemented diet, and (5) survival time was increased in rats bearing F98/hNIS tumors by I-131 treatment. These studies warrant further investigating tumor imaging and therapeutic strategies based on NIS gene transfer followed by radioiodide administration in a variety of human cancers.
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