Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice.
Ovarian cancer represents the fifth leading cause of cancer death among women in the United States, with >16 000 deaths expected this year. This study was carried out to investigate the potential of sodium iodide symporter (NIS)-mediated radioiodide therapy as a novel approach for ovarian cancer treatment. Radioiodide is routinely and effectively used for the treatment of benign and malignant thyroid disease as a result of native thyroidal expression of NIS, which mediates iodide uptake. In vitro gene transfer studies in ovarian cancer cells revealed a 12- and five-fold increase in iodide uptake when transduced with Ad/CMV/NIS or Ad/MUC1/NIS, respectively. Western blot/immunohistochemistry confirmed NIS protein expression. In vivo ovarian tumor xenografts were infected with the adenoviral constructs. (123)I imaging revealed a clear image of the CMV/NIS-transduced tumor, with a less intense image apparent following infection with MUC1/NIS. Therapeutic doses of (131)I following CMV/NIS infection caused a mean 53% reduction in tumor volume (P<0.0001). MUC1/NIS-transduced tumors did not regress, although at 8 weeks following therapy, tumor volume was significantly less that of control animals (166 versus 332%, respectively, P<0.05). This study represents a promising first step investigating the potential for NIS-mediated radioiodide imaging and therapy of ovarian tumors.
Dwyer
R M
RM
Department of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA.
Bergert
E R
ER
O'Connor
M K
MK
Gendler
S J
SJ
Morris
J C
JC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D051379:Mice; D018396:Mucin-1 / Q000235:genetics; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D011401:Promoter Regions, Genetic; D011877:Radionuclide Imaging; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods; D014183:Transplantation, Heterologous; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D018396:Mucin-1; D027981:Symporters; D000099209:Sodium-Iodide Symporters