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 : Official Publication, Society of Nuclear Medicine
Kerstin KnoopChristine Spitzweg

Abstract

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. 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 (123)I scintigraphy, (124)I PET imaging, and (131)I therapy. Results show robust MSC rec...Continue Reading

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Citations

Jan 13, 2016·Stem Cell Research & Therapy·Johannes Leibacher, Reinhard Henschler
Dec 15, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mei Guo, Jun Dou
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Oct 30, 2020·Frontiers in Pharmacology·Giulia GolinelliGiulia Grisendi

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