Sodium Iodide Symporter Gene Transfer for Imaging and Ablation of Prostate Cancer

摘要

The sodium iodide symporter (NIS) mediates iodide uptake in thyroid follicular cells and provides a mechanism for effective radioiodide treatment of residual, recurrent, and metastatic thyroid cancers. The objective of the proposed research is to test the hypothesis that expression of exogenous hNIS in prostatic tissue will enable radioiodide to localize and ablate residual prostate cancer following prostatectomy, such that recurrence and metastasis of the disease can be prevented. The specific aims of this project are to: (1) confirm metastatic progression to distant lymph nodes and lungs following subcutaneous inoculation of rats with MATLyLu prostatic adenocarcinoma cells expressing hNIS; (2) investigate whether radioiodide therapy will prevent metastases and/or prolong survival in rats bearing subcutaneous MATLyLu tumors that express hNIS; (3) determine the expression level of hNIS required to elicit selective radioiodide-mediated killing of MATLyLu-hNlS prostatic adenocarcinoma cells in Vivo: and, (4) restrict hNlS expression in prostatic tissue under transcriptional regulation of prostate-specific promoter.