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Establishment and Characterization of a Breast Cancer Cell Line Expressing Na⁺/I^– Symporters for Radioiodide Concentrator Gene Therapy

Department of Nuclear Medicine and Diagnostic Imaging and Department of Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto; and Department of Radiology, Hamamatsu University School of Medicine, Hamamatsu, Japan

¹³¹I therapy is a widely accepted treatment for metastatic differentiated thyroid cancer. To investigate the feasibility of ¹³¹I therapy for breast cancer, we established breast cancer cells stably expressing Na⁺/I^– symporter (NIS) gene that can be modulated and studied in vitro and in vivo. Methods: We transfected rat NIS genes into a human breast cancer cell line (MCF7) by electroporation. Iodide accumulation was evaluated under various extracellular concentrations of sodium and iodide, and iodide efflux was also assessed. Biodistribution and tumor imaging were studied using tumor-bearing mice. Results: A novel cell line (MCF3B), stably expressing the NIS gene, was established from MCF7. MCF3B took up 44 times more radioiodide in vitro than MCF7 did. Iodide uptake was completely inhibited by 1 mmol/L perchlorate and was dependent on external sodium and iodide concentrations. Iodide efflux from MCF3B cells was slower (half-life [T_1/2] > 27 min) than from FRTL5 thyroid cells (T_1/2 = 4 min). In the biodistribution study using MCF3B-xenografted mice, high tumor uptake of ¹²⁵I was shown (16.73%) at 1 h after injection, and tumor-to-normal tissue ratios were also high (4.84–21.28), except in the stomach (0.47). However, the iodide accumulation in the tumor lessened with time, reaching less than 1% at 24 h after injection. Conclusion: Our preliminary data indicate that NIS-based gene therapy may be applied by concentrating a lethal dose of radiation in tumor cells in vivo, but further investigation is necessary to determine a method of maintaining radioiodine in the cells to allow greater therapeutic effects.

Key Words: sodium iodide symporter • ¹³¹I therapy • breast cancer

Received Dec. 28, 1999; revision accepted Apr. 10, 2000.

For correspondence or reprints contact: Yuji Nakamoto, MD, Department of Nuclear Medicine, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-Ku, Kyoto, 606-8507 Japan.

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