Radioisotope concentrator gene therapy using the sodium/iodide symporter gene.
We demonstrate a novel method of concentrating radiation for tumor imaging or killing. The rat sodium/iodide symporter gene (rNIS) was cloned into a retroviral vector for transfer into cancer cells to mimic the iodide uptake of thyroid follicular cells. In vitro iodide transport shows that the symporter functions similarly in rNIS-transduced tumor cells and rat thyroid follicular cells. rNIS-transduced and control nontransduced (NV) human A375 melanoma xenografts established in vivo in athymic nude mice were imaged using a gamma camera after i.p. injections of 123I. The rNIS-transduced human A375 melanoma tumors are visually distinguishable from and accumulate significantly more radionuclides than NV tumors. In vitro clonogenic assays confirm efficacy and clearly show that rNIS-transduced A375 human melanoma, BNL.1 ME murine transformed liver, CT26 murine colon carcinoma, and IGROV human ovarian carcinoma can be selectively killed by the induced accumulation of 131I. Thus, NIS-based gene therapy may have both diagnostic and therapeutic applications for cancer.
Mandell
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Human Gene Therapy Research Institute, Des Moines, Iowa 50309, USA.
Mandell
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D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007454:Iodides / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D010472:Perchlorates / Q000494:pharmacology; D027981:Symporters; D013667:Technetium / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters