RT Journal Article
SR Electronic
T1 Establishment and Characterization of a Breast Cancer Cell Line Expressing Na<sup>+</sup>/I<sup>−</sup> Symporters for Radioiodide Concentrator Gene Therapy
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1898
OP 1904
VO 41
IS 11
A1 Nakamoto, Yuji
A1 Saga, Tsuneo
A1 Misaki, Takashi
A1 Kobayashi, Hisataka
A1 Sato, Noriko
A1 Ishimori, Takayoshi
A1 Kosugi, Shinji
A1 Sakahara, Harumi
A1 Konishi, Junji
YR 2000
UL http://jnm.snmjournals.org/content/41/11/1898.abstract
AB 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 [T1/2] &gt; 27 min) than from FRTL5 thyroid cells (T1/2 = 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.