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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/16908

Title: Optimization of Multimodal Imaging of Mesenchymal Stem Cells Using the Human Sodium Iodide Symporter for PET and Cerenkov Luminescence Imaging
Authors: Wolfs, Esther
Holvoet, Bryan
Gijsbers, Rik
Casteels, Cindy
Roberts, Scott J.
Maris, Michael
Ibrahimi, Abdelilah
Debyser, Zeger
Van Laere, Koen
Verfaillie, Catherine M.
Deroose, Christophe M.
Issue Date: 2014
Citation: PLOS ONE, 9 (4)
Abstract: Purpose: The use of stably integrated reporter gene imaging provides a manner to monitor the in vivo fate of engrafted cells over time in a non-invasive manner. Here, we optimized multimodal imaging (small-animal PET, Cerenkov luminescence imaging (CLI) and bioluminescence imaging (BLI)) of mesenchymal stem cells (MSCs), by means of the human sodium iodide symporter (hNIS) and firefly luciferase (Fluc) as reporters. Methods: First, two multicistronic lentiviral vectors (LV) were generated for multimodal imaging: BLI, 124I PET/SPECT and CLI. Expression of the imaging reporter genes was validated in vitro using 99mTcO4 2 radioligand uptake experiments and BLI. Uptake kinetics, specificity and tracer elution were determined as well as the effect of the transduction process on the cell’s differentiation capacity. MSCs expressing the LV were injected intravenously or subcutaneously and imaged using smallanimal PET, CLI and BLI. Results: The expression of both imaging reporter genes was functional and specific. An elution of 99mTcO4 2 from the cells was observed, with 31% retention after 3 h. After labeling cells with 124I in vitro, a significantly higher CLI signal was noted in hNIS expressing murine MSCs. Furthermore, it was possible to visualize cells injected intravenously using BLI or subcutaneously in mice, using 124I small-animal PET, CLI and BLI. Conclusions: This study identifies hNIS as a suitable reporter gene for molecular imaging with PET and CLI, as confirmed with BLI through the expression of Fluc. It supports the potential for a wider application of hNIS reporter gene imaging and future clinical applications.
URI: http://hdl.handle.net/1942/16908
DOI: 10.1371/journal.pone.0094833
ISI #: 000335226500037
ISSN: 1932-6203
Category: A1
Type: Journal Contribution
Validation: ecoom, 2015
Appears in Collections: Research publications

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