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In vivo molecular imaging and radionuclide (131I) therapy of human nasopharyngeal carcinoma cells transfected with a lentivirus expressing sodium iodide symporter.

Shi S, Zhang M, Guo R, Miao Y, Hu J, Xi Y, Li B - PLoS ONE (2015)

Bottom Line: In vitro, 131I significantly reduced the clonogenic survival of CNE-2Z-NIS cells.Lentiviruses effectively delivered and mediated long-lasting expression of NIS in CNE-2Z cells which enabled uptake and accumulation of radioisotopes and provided a significant therapeutic effect in an in vivo model of NPC.NIS-mediated radioiodine treatment merits further investigation as a potentially effective, low toxicity therapeutic strategy for NPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.

ABSTRACT

Introduction: Despite recent improvements in the survival rates for nasopharyngeal carcinoma (NPC), novel treatment strategies are required to improve distant metastasis-free survival. The sodium iodine symporter (NIS) gene has been applied for in vivo imaging and cancer therapy. In this study, we examined the potential of NIS gene therapy as a therapeutic approach in NPC by performing non-invasive imaging using 125I and 131I therapy in vivo.

Methods: We constructed a lentiviral vector expressing NIS and enhanced green fluorescent protein (EGFP) under the control of the human elongation factor-1α (EF1α) promoter, and stably transfected the vector into CNE-2Z NPC cells to create CNE-2Z-NIS cells. CNE-2Z and CNE-2Z-NIS tumor xenografts were established in nude mice; 125I uptake, accumulation and efflux were measured using micro-SPECT/CT imaging; the therapeutic effects of treatment with 131I were assessed over 25 days by measuring tumor volume and immunohistochemical staining of the excised tumors.

Results: qPCR, immunofluorescence and Western blotting confirmed that CNE-2Z-NIS cells expressed high levels of NIS mRNA and protein. CNE-2Z-NIS cells and xenografts took up and accumulated significantly more 125I than CNE-2Z cells and xenografts. In vitro, 131I significantly reduced the clonogenic survival of CNE-2Z-NIS cells. In vivo, 131I effectively inhibited the growth of CNE-2Z-NIS xenografts. At the end of 131I therapy, CNE-2Z-NIS xenograft tumor cells expressed higher levels of NIS and caspase-3 and lower levels of Ki-67.

Conclusion: Lentiviruses effectively delivered and mediated long-lasting expression of NIS in CNE-2Z cells which enabled uptake and accumulation of radioisotopes and provided a significant therapeutic effect in an in vivo model of NPC. NIS-mediated radioiodine treatment merits further investigation as a potentially effective, low toxicity therapeutic strategy for NPC.

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Quantitative analysis of 125I uptake in vivo.Conc values (μCi/mm3) of the xenograft tumors and organs after injection of 125I (same time points as in Fig. 4).
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pone.0116531.g005: Quantitative analysis of 125I uptake in vivo.Conc values (μCi/mm3) of the xenograft tumors and organs after injection of 125I (same time points as in Fig. 4).

Mentions: ROIs were created by CT positioning during SPECT imaging to define the tissues described above and the Conc values were obtained at various time points. Accumulation of 125I increased gradually in CNE-2Z-NIS tumors and reached the highest Conc value at 4 h after injection of 125I; this was significantly (up to 75%) higher than the corresponding values for CNE-2Z tumors. And then decreased by 8 h and reached the lowest Conc value at 32 h. Significant radioiodine accumulation was also observed in tissues which express endogenous NIS, including the thyroid and stomach, and also in the urinary bladder and heart due to renal elimination and absorption of the radionuclide into the bloodstream. The Conc values of the lung, liver, muscle and the intestine remained low at all time points (Fig. 5).


In vivo molecular imaging and radionuclide (131I) therapy of human nasopharyngeal carcinoma cells transfected with a lentivirus expressing sodium iodide symporter.

Shi S, Zhang M, Guo R, Miao Y, Hu J, Xi Y, Li B - PLoS ONE (2015)

Quantitative analysis of 125I uptake in vivo.Conc values (μCi/mm3) of the xenograft tumors and organs after injection of 125I (same time points as in Fig. 4).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4306548&req=5

pone.0116531.g005: Quantitative analysis of 125I uptake in vivo.Conc values (μCi/mm3) of the xenograft tumors and organs after injection of 125I (same time points as in Fig. 4).
Mentions: ROIs were created by CT positioning during SPECT imaging to define the tissues described above and the Conc values were obtained at various time points. Accumulation of 125I increased gradually in CNE-2Z-NIS tumors and reached the highest Conc value at 4 h after injection of 125I; this was significantly (up to 75%) higher than the corresponding values for CNE-2Z tumors. And then decreased by 8 h and reached the lowest Conc value at 32 h. Significant radioiodine accumulation was also observed in tissues which express endogenous NIS, including the thyroid and stomach, and also in the urinary bladder and heart due to renal elimination and absorption of the radionuclide into the bloodstream. The Conc values of the lung, liver, muscle and the intestine remained low at all time points (Fig. 5).

Bottom Line: In vitro, 131I significantly reduced the clonogenic survival of CNE-2Z-NIS cells.Lentiviruses effectively delivered and mediated long-lasting expression of NIS in CNE-2Z cells which enabled uptake and accumulation of radioisotopes and provided a significant therapeutic effect in an in vivo model of NPC.NIS-mediated radioiodine treatment merits further investigation as a potentially effective, low toxicity therapeutic strategy for NPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.

ABSTRACT

Introduction: Despite recent improvements in the survival rates for nasopharyngeal carcinoma (NPC), novel treatment strategies are required to improve distant metastasis-free survival. The sodium iodine symporter (NIS) gene has been applied for in vivo imaging and cancer therapy. In this study, we examined the potential of NIS gene therapy as a therapeutic approach in NPC by performing non-invasive imaging using 125I and 131I therapy in vivo.

Methods: We constructed a lentiviral vector expressing NIS and enhanced green fluorescent protein (EGFP) under the control of the human elongation factor-1α (EF1α) promoter, and stably transfected the vector into CNE-2Z NPC cells to create CNE-2Z-NIS cells. CNE-2Z and CNE-2Z-NIS tumor xenografts were established in nude mice; 125I uptake, accumulation and efflux were measured using micro-SPECT/CT imaging; the therapeutic effects of treatment with 131I were assessed over 25 days by measuring tumor volume and immunohistochemical staining of the excised tumors.

Results: qPCR, immunofluorescence and Western blotting confirmed that CNE-2Z-NIS cells expressed high levels of NIS mRNA and protein. CNE-2Z-NIS cells and xenografts took up and accumulated significantly more 125I than CNE-2Z cells and xenografts. In vitro, 131I significantly reduced the clonogenic survival of CNE-2Z-NIS cells. In vivo, 131I effectively inhibited the growth of CNE-2Z-NIS xenografts. At the end of 131I therapy, CNE-2Z-NIS xenograft tumor cells expressed higher levels of NIS and caspase-3 and lower levels of Ki-67.

Conclusion: Lentiviruses effectively delivered and mediated long-lasting expression of NIS in CNE-2Z cells which enabled uptake and accumulation of radioisotopes and provided a significant therapeutic effect in an in vivo model of NPC. NIS-mediated radioiodine treatment merits further investigation as a potentially effective, low toxicity therapeutic strategy for NPC.

Show MeSH
Related in: MedlinePlus