Journal of Nuclear Medicine | |
Mesenchymal Stem Cell–Mediated, Tumor Stroma–Targeted Radioiodine Therapy of Metastatic Colon Cancer Using the Sodium Iodide Symporter as Theranostic Gene | |
Burkhard Göke1  Kerstin Knoop1  Kathrin Schmohl1  Peter J. Nelson1  Ernst Wagner1  Clemens Cyran1  Guido Böning1  Andrea Müller1  Christine Spitzweg1  Nathalie Schwenk1  Peter Bartenstein1  Christian Zach1  Janette Carlsen1  | |
关键词: sodium iodide symporter; mesenchymal stem cells; hepatic metastases; colon cancer; gene therapy; RANTES; | |
DOI : 10.2967/jnumed.114.146662 | |
学科分类:医学(综合) | |
来源: Society of Nuclear Medicine | |
【 摘 要 】
The tumor-homing property of mesenchymal stem cells (MSCs) allows targeted delivery of therapeutic genes into the tumor microenvironment. The application of sodium iodide symporter (NIS) as a theranostic gene allows noninvasive imaging of MSC biodistribution and transgene expression before therapeutic radioiodine application. We have previously shown that linking therapeutic transgene expression to induction of the chemokine CCL5/RANTES allows a more focused expression within primary tumors, as the adoptively transferred MSC develop carcinoma-associated fibroblast-like characteristics. Although RANTES/CCL5-NIS targeting has shown efficacy in the treatment of primary tumors, it was not clear if it would also be effective in controlling the growth of metastatic disease. Methods: To expand the potential range of tumor targets, we investigated the biodistribution and tumor recruitment of MSCs transfected with NIS under control of the RANTES/CCL5 promoter (RANTES-NIS-MSC) in a colon cancer liver metastasis mouse model established by intrasplenic injection of the human colon cancer cell line LS174t. RANTES-NIS-MSCs were injected intravenously, followed by 123I scintigraphy, 124I PET imaging, and 131I therapy. Results: Results show robust MSC recruitment with RANTES/CCL5-promoter activation within the stroma of liver metastases as evidenced by tumor-selective iodide accumulation, immunohistochemistry, and real-time polymerase chain reaction. Therapeutic application of 131I in RANTES-NIS-MSC–treated mice resulted in a significant delay in tumor growth and improved overall survival. Conclusion: This novel gene therapy approach opens the prospect of NIS-mediated radionuclide therapy of metastatic cancer after MSC-mediated gene delivery.
【 授权许可】
Unknown
【 预 览 】
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RO201912010199511ZK.pdf | 1073KB | download |