Abstract
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Objectives: To test the feasibility of using Survivin promoter to induce human sodium iodide symporter (NIS) expression in prostate cancer for 131I therapy and 99mTcO4 tumor imaging.
Methods: We constructed and packaged adenovirus Ad-Sur-NIS containing the survivin promoter and NIS gene, and Ad-CMV-NIS cotaining the CMV promoter and NIS gene used as a positive control. After infected LNCaP, DU145, PC-3 prostate cancer cell lines and DPC human normal dental pulp cells, NIS expression was analyzed by western blot. Functional experiments in vitro such as 125I and 99mTcO4 uptake, perchlorate anions inhibition 125I uptake, cell killing with 131I and clonogenic assay were done.PC-3 prostate cancer xenografts established in vivo in athymic nude mice were imaged using 99mTcO4 48h after i.v. injection of Ad-Sur-NIS.
Results: WB showed that NIS expression in prostate cancer cell lines but no in DFC after infection of Ad-Sur-NIS virus. Uptake of 125I and 99mTcO4 were increased ~50-fold by Ad-Sur-NIS and ~100-fold by Ad-CMV-NIS, no significant uptake in DFC compared with blank control. ClO4- (300uM) could inhibited more than 90% 125I uptake. In vitro clonogenic assays showed that Ad-Sur-NIS virus infected LNCaP, DU145 and PC-3 could be selectively killed by 131I (86%, 90% and 92%, respectively) while less effect on DFC(<10%). The tumors were visually distinguishable from and accumulate significantly more radionuclides than normal tissues apart from thyroid, stomach, kidney and bladder.
Conclusions: These results indicate that Ad-Sur-NIS can be used to achieve high-magnitude and tissue-specific expression of NIS in prostate tissue and is a promising candidate for cancer gene therapy and imaging.
Research Support: By National Natural Science Foundation of China No. 30672132
- Society of Nuclear Medicine, Inc.