Genetically Targeted Radiotherapy Utilizing the Human Sodium Iodide Symporter in Human Breast Carcinoma Cells

摘要

The purpose of this proposal was to elaborate on the viability of NIS-mediated genetically targeted radiotherapy as a possible novel therapeutic intervention in human breast carcinoma. Problems encountered with SK- Pr-3 forced other cell limes to be utilized for tumor growth and imaging. A stable NIS expressing clone was derived from SK-Pr-3 cell lime. The ability of the clone to accumulate radioactivity was lost after several passages, which may be due to epigenetically silencing. The NIS expressing clone was unable to accumulate radioactivity in vitro. The acquisition of a pin-hole collimator enables mice bearing Ad-NIS treated tumors to be non-invasively imaged following radioactive administration. The imaging enables dosimetric calculation to be performed to determine the absorbed dose to the tumor. Correlations between the absorbed dose and therapeutic outcome can provide a possible prediction of tumor response. Real-time RT-PCR experiments were used to detect increased NIS expression after treatment with several histone deactylase inhibitors (NDACi), including sodium butyrate (SR), trichostatin A (TSA), in conjunction with the DNA methyltransferase inhibitor 5-aza- 2'deoxycytidine.