Mesenchymal Stem Cell–Mediated, Tumor Stroma–Targeted Radioiodine Therapy of Metastatic Colon Cancer Using the Sodium Iodide Symporter as Theranostic Gene

Journal of Nuclear Medicine

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