Imaging Early Fate of Cancer Stem Cells in Mouse Hindlimbs with Sodium Iodide Symporter Gene and I-124 PET

Purpose: We investigated the capacity of sodium/iodide symporter (NIS) positron emission tomography (PET) to image and quantitate early engraftment and survival of cancer stem cells (CSCs) in living mice. Procedures: CT26 colon cancer cells and CSCs were infected with an adenovirus expressing both NIS and enhanced green fluorescent protein (EGFP). Cells were implanted into normal and ischemic hindlimbs of mice, and serial optical and I-124 PET imaging was performed. Extracted tissues underwent I-124 measurements and confocal microscopy. Results: NIS.EGFP gene transfer increased fluorescence and I-124 uptake of CSCs and CT26 cells without adverse effects. I-124 PET clearly visualized implanted tumor cells in vivo, whereas optical imaging was suboptimal. PET revealed 1.95, 2.22, and 1.93-fold greater I-124 uptake by CSC inoculation into ischemic compared to non-ischemic limbs at 2, 15, and 24 h, respectively. CT26 cells showed similar but smaller differences. PET findings were confirmed by ex vivo measurements and confocal microscopy. Conclusions: NIS PET can help identify microenvironment conditions that influence early survival of implanted CSCs.