Abstract
We sought to evaluate the feasibility of molecular imaging using the human sodium iodide symporter (hNIS) gene as a reporter, in addition to the enhanced firefly luciferase (effluc) gene, for tracking dendritic cell (DCs) migration in living mice. A murine dendritic cell line (DC2.4) co-expressing hNIS and effluc genes (DC/NF) was established. For the DC-tracking study, mice received either parental DCs or DC/NF cells in the left or right footpad, respectively, and combined I-124 PET/CT and bioluminescence imaging (BLI) were performed. In vivo PET/CT imaging with I-124 revealed higher activity of the radiotracer in the draining popliteal lymph nodes (DPLN) of the DC/NF injection site at day 1 than DC injection site (p < 0.05). The uptake value further increased at day 4 (p < 0.005). BLI also demonstrated migration of DC/NF cells to the DPLNs at day 1 post-injection, and signals at the DPLNs were much higher at day 4. These data support the feasibility of hNIS reporter gene imaging in the tracking of DC migration to lymphoid organs in living mice. DCs expressing the NIS reporter gene could be a useful tool to optimize various strategies of cell-based immunotherapy.
Highlights
Several imaging techniques for imaging Dendritic cells (DCs) migration have been reported, including gamma scintigraphy with In-1115, positron emission tomography (PET) with F-186, magnetic resonance imaging (MRI) using iron oxide magnetic nanoparticles[7,8], near-infrared nanoparticles[9], and reporter gene-based imaging[10,11]
Tumor antigen-loaded DCs were recently reported to be used as a cancer vaccine to prevent tumors or eradicate existing tumors, encouraging many clinical trials evaluating the possibility of using DCs to generate an immune response against tumor-specific or tumor-associated antigens in lung cancer, melanoma, and colon cancer[32]
Similar to the luciferase and HSV1-tk genes that are extensively investigated for their use in cell tracking, the NIS gene has been demonstrated to be an attractive reporter gene for monitoring cancer progression and therapeutic response[33,34,35,36], stem cell trafficking[37,38], and specific cellular events[39,40] in living subjects
Summary
Several imaging techniques for imaging DC migration have been reported, including gamma scintigraphy with In-1115, positron emission tomography (PET) with F-186, magnetic resonance imaging (MRI) using iron oxide magnetic nanoparticles[7,8], near-infrared nanoparticles[9], and reporter gene-based imaging[10,11]. Nuclear medicine imaging with direct or indirect labeling provide high sensitivity without depth limitation, and allows pharmacodynamics (PD)/pharmacokinetics (PK) study because of its ability of quantitative analysis. It has low spatial resolution and concern about radiation safety[12,13,14]. The NIS reporter gene is non-immunogenic and has no known adverse effects on cell viability and function, and this imaging technique does not require complex probe synthesis These advantages of the NIS gene led us to further investigate whether the gene could be used for DC tracking in living organisms. Serial BLI and I-124 PET/CT imaging were performed to assess the initial distribution and subsequent migration of infused DCs toward draining lymph nodes in living mice
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