Genetically Targeted Radiotherapy Utilizing the Human Sodium Iodide Symporter in Human Breast Carcinoma Cells
Abstract
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 transfection of SK-Br-3 forced other cell lines to be utilized in the development of stable NIS-expressing clones while continuing to try other transfection methods. Stable NIS-expressing clone was derived from MDA-MB-435 cell line. 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 or in vivo. Real-time RT-PCR experiments are examining the detection of NIS expression after retinoic acid treatments. This treatment may turn on lactoperoxidase expression as well, increasing the retention of radioactivity in the tumor. LPO treatment did increase retention of I-125 in Ad-NIS treated cells compared to Ad-NIS treatment alone. 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA436156
Entities
People
- Frederick E. Domann
- Kimberly J. Krager
Organizations
- University of Iowa