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Radioiodide Treatment after Sodium Iodide Symporter Gene Transfer Is a Highly Effective Therapy in Neuroendocrine Tumor Cells¹

Departments of Nuclear Medicine [M. L. S., A. W., M. B., T. M. B.], Gastroenterology, Endocrinology, and Metabolism [R. G., W. J., H. S., T. B., B. S., R. A., A. E. H.], and Clinical Research Unit for Gastrointestinal Endocrinology [R. G., H. S.], Philipps University Marburg, 35043 Marburg, Germany

This study evaluates the possibility of treating Bon1 and QGP pancreatic neuroendocrine tumor cells with radioactive iodide (¹³¹I) after stable transfection with the thyroid sodium iodide symporter (NIS). NIS expression was driven either by the strong viral cytomegalovirus promoter or by the tissue-specific chromogranin A promoter. Using either approach, NIS expression was confirmed by reverse transcription-PCR and Western blotting. Uptake of radioactive iodide was increased 20-fold by chromogranin A promoter-driven NIS expression and 50-fold by cytomegalovirus promoter-driven NIS expression. Maximal uptake was reached within 15 min in QGP cells and 30 min in Bon1 cells. Effective half-life was 5 min in QGP and 30 min in Bon1 cells. No evidence of organification was detected by high-performance liquid chromatography and gel filtration chromatography. ¹³¹I was a highly effective treatment in NIS-expressing QGP and Bon1 cells, reducing clone formation by 99.83 and 98.75%, respectively, in the in vitro clonogenic assay. In contrast, clone formation was not reduced in QGP and Bon1 cells without NIS expression after incubation with the same activity concentration of ¹³¹I as compared with mock treated cells. Absorbed doses to QGP and Bon1 cells are up to 150 and 30 Gy, respectively. In addition, a direct cytotoxic effect of radioiodide was demonstrated in NIS-expressing Bon1 cells after ¹³¹I incubation. In conclusion, radioiodide treatment after NIS gene transfer appears to be a promising novel approach in the therapy of neuroendocrine tumors if its highly encouraging in vitro effectiveness can be transferred to the in vivo situation.

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