Abstract |
Radioiodide uptake in thyroid follicular epithelial cells, mediated by a plasma membrane transporter, sodium
iodide symporter (NIS), provides a first step mechanism for thyroid cancer detection by radioiodide injection and
effective radioiodide treatment for patients with invasive, recurrent, and/or metastatic thyroid cancers after total
thyroidectomy. NIS gene transfer to tumor cells may significantly and specifically enhance internal radioactive
accumulation of tumors following radioiodide administration, and result in better tumor control. NIS gene
transfers have been successfully performed in a variety of tumor animal models by either plasmid-mediated
transfection or virus (adenovirus or retrovirus)-mediated gene delivery. These animal models include nude mice
xenografted with human melanoma, glioma, breast cancer or prostate cancer, rats with subcutaneous thyroid
tumor implantation, as well as the rat intracranial glioma model. In these animal models, non-invasive imaging of
in vivo tumors by gamma camera scintigraphy after radioiodide or technetium injection has been performed
successfully, suggesting that the NIS can serve as an imaging reporter gene for gene therapy trials. In addition,
the tumor killing effects of I-131, ReO4-188 and At-211 after NIS gene transfer have been demonstrated in in vitro
clonogenic assays and in vivo radioiodide therapy studies, suggesting that NIS gene can also serve as a
therapeutic agent when combined with radioiodide injection. Better NIS-mediated imaging and tumor treatment by
radioiodide requires a more efficient and specific system of gene delivery with better retention of radioiodide in
tumor. Results thus far are, however, promising, and suggest that NIS gene transfer followed by radioiodide
treatment will allow non-invasive in vivo imaging to assess the outcome of gene therapy and provide a
therapeutic strategy for a variety of human diseases. (Korean J Nucl Med 38(2):152-160, 2004) |