Experimental study of nasopharyngeal carcinoma radionuclide imaging and therapy using transferred human sodium/iodide symporter gene

PLoS One. 2015 Jan 23;10(1):e0117053. doi: 10.1371/journal.pone.0117053. eCollection 2015.

Abstract

Purpose: The aim of this study was to design a method of radionuclide for imaging and therapy of nasopharyngeal carcinoma (NPC) using the transferred human sodium/iodide symporter (hNIS) gene.

Methods: A stable NPC cell line expressing hNIS was established (CNE-2-hNIS). After 131I treatment, we detected proliferation and apoptosis of NPC cells, both in vitro and vivo. In vivo, the radioactivity of different organs of nude mice was counted and (99m)Tc imaging using SPECT was performed. The apparent diffusion coefficient (ADC) value changes of tumor xenografts were observed by diffusion-weighted magnetic resonance imaging (DW-MRI) within 6-24 days of 131I treatment. The correlation of ADC changes with apoptosis and proliferation was investigated. Post-treatment expression levels of P53, Bax, Bcl-2, Caspase-3, and Survivin proteins were detected by western blotting.

Results: 131I uptake was higher in CNE-2-hNIS than in CNE-2 cells. The proliferation and apoptosis rate decreased and increased respectively both in vitro and vivo in the experimental group after 131I treatment. The experimental group tumors accumulated (99m)Tc in vivo, leading to a good visualization by SPECT. DW-MRI showed that ADC values increased in the experimental group 6 days after treatment, while ADC values were positively and negatively correlated with the apoptotic and Ki-67 proliferation indices, respectively. After treatment, CNE-2-hNIS cells up-regulated the expression of P53 and Survivin proteins and activated Caspase-3, and down-regulated the expression of Bcl-2 proteins.

Conclusions: The radionuclide imaging and therapy technique for NPC hNIS-transfected cell lines can provide a new therapy strategy for monitoring and treatment of NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diffusion Magnetic Resonance Imaging / methods*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Iodine Radioisotopes / administration & dosage*
  • Iodine Radioisotopes / pharmacokinetics
  • Mice
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / diagnostic imaging*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy*
  • Neoplasm Transplantation
  • Radionuclide Imaging
  • Radiopharmaceuticals / metabolism
  • Sodium Pertechnetate Tc 99m / metabolism
  • Symporters / genetics
  • Symporters / metabolism*
  • Transfection

Substances

  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Symporters
  • sodium-iodide symporter
  • Sodium Pertechnetate Tc 99m

Grants and funding

This work was supported by Guangdong Provincial Science and Technology Project—Project Government’s commitment to a particular task (2011B061200028), and the major science and technology projects of Guangdong Province (2003 A3080501). Guangdong Province Medical Research Foundation (A2012342). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.