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 o f radioiodine therapy of prostate cancer. Therefore, we investigated radioi odine accumulation and therapeutic effectiveness of I-131 in NIS-transfecte d prostate cancer cells in vitro and in vivo. The human prostatic adenocarc inoma cell line LNCaP was stably transfected with NIS cDNA under the contro l of the prostate-specific antigen promoter. The stably transfected LNCaP c ell line NP-1 showed perchlorate-sensitive, androgen-dependent iodide uptak e in vitro that resulted in selective killing of these cells by I-131 in an in vitro clonogenic assay. Xenografts were established in athymic nude mic e and imaged using a gamma camera after i.p. injection of 500 mu Ci of I-12 3, In contrast to the NIS-negative control tumors (P-l) which showed no in vivo uptake of I-123, NP-I tumors accumulated 25-30% of the total I-123 adm inistered with a biological half-life of 45 h, In addition, NIS protein exp ression in LNCaP cell xenografts was confirmed by Western blot analysis and immunohistochemistry. After a single i.p. application of a therapeutic I-1 31 dose (3 mCi), significant tumor reduction was achieved in NP-I tumors in the therapy group compared with P-l tumors and tumors in the control group . In conclusion, a therapeutic effect of I-131 has been demonstrated in pro state cancer cells after induction of tissue-specific iodide uptake activit y by prostate-specific antigen promoter-directed NIS expression in vitro an d in vivo. This study demonstrates the potential of NIS as a novel therapeu tic gene for nonthyroidal cancers, in particular prostate cancer.