In vivo Molecular Imaging and Radionuclide (131I) Therapy of Human Nasopharyngeal Carcinoma Cells Transfected with a Lentivirus Expressing Sodium Iodide Symporter

Abstract

IntroductionDespite 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.MethodsWe 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.ResultsqPCR, 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.ConclusionLentiviruses 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.

Bone Marrow–Derived Mesenchymal Stem Cell–Mediated Dual-Gene Therapy for Glioblastoma

“…10,11 NIS is involved in the uptake of several isotopes, including 125 I, 99m Tc, 188 Re, and 131 I. 12 131 I radioiodine therapy mediated by NIS has been shown to be a safe and effective approach for the imaging and treatment of thyroid disease. 13 The authors and other researchers have successfully introduced ectopic expression of NIS by virus for imaging and therapy in nonthyroidal carcinoma.…”

Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas

“…Concurrently, radiotherapy that delivers cytotoxic levels of energy from radionuclides to disease sites has been used to treat various tumors. , Many radionuclides including 131 I, phosphorus-32 ( 32 P), strontium-89 ( 89 Sr), yittrium-90 ( 90 Y), and rhenium-188 ( 188 Re) have been applied for radiotherapy in the clinic. Among these, 131 I has been received considerable attention because of its relative long half-life ( t 1/2 = 8.01 days), appropriate radiation energy (0.606 MeV, 89.9%), and convenient labeling methods. − Furthermore, 131 I has also been used for SPECT imaging, enabling simultaneous radionuclide imaging and radiotherapy. − However, because of the specific affinity of free 131 I for the thyroid, free 131 I is difficult to directly accumulate within the tumor site to achieve effective SPECT imaging and radiotherapy. Thus, it is critical to select an appropriate carrier system to specifically deliver 131 I to the tumor site.…”

“…31-34 Furthermore, 131 I has also been used for SPECT imaging, enabling simultaneous radionuclide imaging and radiotherapy. [35][36][37] However, due to the specific affinity of free 131 I for the thyroid, free 131 I is difficult to directly accumulate within the tumor site to achieve effective SPECT imaging and radiotherapy. Thus, it is critical to select an appropriate carrier system to specifically deliver 131 I to the tumor site.…”

131I therapy mediated by sodium/iodide symporter combined with kringle 5 has a synergistic therapeutic effect on glioma

“…We determined 125 I uptake and efflux in triplicate as previously described (17). The day before the experiment, U87-K5-NIS, U87-K5-GfP, U87-GfP-NIS and U87 cells were plated (2x10 5 cells/well) into 24-well plates.…”