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

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.

• Authors: Shuo Shi, Min Zhang, Rui Guo, Ying Miao, Jiajia Hu, Yun Xi, Biao Li
• Journal: PloS one (PLoS One) Vol. 10 Issue 1 Pg. e0116531 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25621996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Iodine Radioisotopes
• Radioisotopes
• Symporters
• sodium-iodide symporter

Topics

• Animals
• Carcinoma
• Cell Line, Tumor
• Genetic Therapy
• Humans
• Iodine Radioisotopes (pharmacology, therapeutic use)
• Lentivirus (genetics)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (therapy)
• Radioisotopes (pharmacology, therapeutic use)
• Symporters (biosynthesis, genetics)
• Tissue Distribution
• Transfection
• Xenograft Model Antitumor Assays