Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter.
Causing prostate cancer cells to express functionally active sodium iodide symporter (NIS) by targeted NIS gene transfer might offer the possibility of radioiodine therapy of prostate cancer. Therefore, we investigated radioiodine accumulation and therapeutic effectiveness of 131I in NIS-transfected prostate cancer cells in vitro and in vivo. The human prostatic adenocarcinoma cell line LNCaP was stably transfected with NIS cDNA under the control of the prostate-specific antigen promoter. The stably transfected LNCaP cell line NP-1 showed perchlorate-sensitive, androgen-dependent iodide uptake in vitro that resulted in selective killing of these cells by 131I in an in vitro clonogenic assay. Xenografts were established in athymic nude mice and imaged using a gamma camera after i.p. injection of 500 microCi of 123I. In contrast to the NIS-negative control tumors (P-1) which showed no in vivo uptake of 123I, NP-1 tumors accumulated 25-30% of the total 123I administered with a biological half-life of 45 h. In addition, NIS protein expression in LNCaP cell xenografts was confirmed by Western blot analysis and immunohistochemistry. After a single i.p. application of a therapeutic 131I dose (3 mCi), significant tumor reduction was achieved in NP-1 tumors in the therapy group compared with P-1 tumors and tumors in the control group. In conclusion, a therapeutic effect of 131I has been demonstrated in prostate cancer cells after induction of tissue-specific iodide uptake activity by prostate-specific antigen promoter-directed NIS expression in vitro and in vivo. This study demonstrates the potential of NIS as a novel therapeutic gene for nonthyroidal cancers, in particular prostate cancer.
Spitzweg
C
C
Department of Endocrinology, Mayo Clinic, Rochester, Minnesota 55905, USA. spitzweg.christine@mayo.edu
O'Connor
M K
MK
Bergert
E R
ER
Tindall
D J
DJ
Young
C Y
CY
Morris
J C
JC
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D027981:Symporters; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters