In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas

Abstract

Radioactive iodide uptake (RAIU)

Effects of dose, intervention time, and radionuclide on sodium iodide symporter (NIS)-targeted radionuclide therapy

“…In our previous study, we showed that ex vivo NIS gene transfer to F98 rat glioma cells conferred a moderate survival benefit in 131 I-treated rats bearing intracerebral F98/hNIS gliomas. 5 In the present study, we show that the 131 …”

“…5 The finding that 131 I therapeutic effectiveness in F98/hNIS gliomas was dose-dependent suggests that dose escalation could further improve the efficacy of NIS-targeted 131 I therapy. The validation of NIS-targeted 131 I therapy in another animal model further supports our hypothesis that NIS-mediated radionuclide therapy may be useful to circumvent the problem of a narrow therapeutic window intrinsic to brain tumor radiotherapy.…”

“…NIS gene transfer has been demonstrated to increase radioactive iodine uptake (RAIU) up to several hundredfold in a variety of cell types. [3][4][5][6] In addition to allowing in vivo tumor imaging, [5][6][7][8][9] NIS gene transfer into tumor cells also renders them susceptible to being killed in vitro by 131 I. 4,10,11 However, lack of iodine organification in NIS-transduced tumors has raised concerns about the ultimate effectiveness of NIS-mediated radionuclide therapy for nonthyroidal malignancies, as an insufficient tumor radiation absorbed dose 8,9 may result from short radionuclide retention time.…”

Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

“…8 Recent developments in gene therapy have led to a number of studies aimed at introducing NIS expression in other tumor types, to provide for radioiodide imaging and therapy. [9][10][11][12][13][14][15][16] The ability to introduce NIS expression into ovarian tumors would be highly beneficial. Along with an extended proven record in radioiodide therapy of thyroid disease, NIS offers a major advantage as a therapeutic gene because it provides for imaging to confirm targeted expression of the protein before proceeding to therapy.…”

Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth

“…30 The human sodium-iodide symporter (hNIS) is a transmembrane ion symporter that concentrates iodide in thyroid follicular cells and is being evaluated as a therapeutic gene for the treatment for cancer. 31,32 To facilitate the noninvasive monitoring of oncolytic MV and to enhance its oncolytic efficiency, the virus was engineered to express hNIS (MV-NIS). Radioiodine was concentrated in MV-NIS-infected cells and the concentration of radioiodine increased as the MV-NIS infection progressed.…”