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OtherBASIC SCIENCE INVESTIGATIONS

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

Yuji Nakamoto, Tsuneo Saga, Takashi Misaki, Hisataka Kobayashi, Noriko Sato, Takayoshi Ishimori, Shinji Kosugi, Harumi Sakahara and Junji Konishi
Journal of Nuclear Medicine November 2000, 41 (11) 1898-1904;
Yuji Nakamoto
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Tsuneo Saga
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Takashi Misaki
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Hisataka Kobayashi
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Noriko Sato
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Takayoshi Ishimori
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Shinji Kosugi
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Harumi Sakahara
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Junji Konishi
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  • FIGURE 1.
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    FIGURE 1.

    Time course of iodide uptake by MCF3B without perchlorate, MCF3B with 1 mmol/L perchlorate, and MCF7 without perchlorate. All data are expressed as means (pmol/106 cells) of duplicate wells. Iodide uptake by MCF3B was rapid and became maximal within 30 min, whereas uptake by MCF3B with perchlorate and by MCF7 remained low.

  • FIGURE 2.
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    FIGURE 2.

    Iodide uptake plotted against Na+ concentration (A), I− concentration (B), and cell numbers (C).

  • FIGURE 3.
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    FIGURE 3.

    Iodide efflux from MCF3B and FRTL5 cells. All data are expressed as means (remaining percentage of 125I−) of duplicate wells. Although iodide that accumulated in FRTL5 cells was rapidly exchangeable, MCF3B cells released 125I− more slowly.

  • FIGURE 4.
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    FIGURE 4.

    Tumor-to-normal tissue ratios. High ratios were obtained as early as 1 h after injection, except in stomach.

  • FIGURE 5.
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    FIGURE 5.

    Time course of decay-corrected iodide accumulation in subcutaneous tumors. At 24 h after administration of 125I−, uptake in tumor was reduced to 0.2%. Monoexponential curve fitted for each point was also shown on identical graph. Calculated effective T1/2 was 3.59 h.

  • FIGURE 6.
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    FIGURE 6.

    Imaging of MCF3B tumors by gamma camera. Two hours after injection of Na131I (11.1 MBq) intravenously, planar image (B) of mouse was obtained. Note visualized NIS-transduced MCF3B tumor (T). Thyroid, stomach, and bladder were also detected by physiologic uptake. Planar image is to scale with photograph (A).

  • FIGURE 7.
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    FIGURE 7.

    Relationship between radius of tumor and estimated dose for 3.7 MBq 131I administration. Dose increased with increase in radius of tumor but was considered to be therapeutically insufficient.

Tables

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    TABLE 1.

    Biodistribution Data for Tumor-Bearing Nude Mice

    Site1 h3 h6 h12 h24 h
    Blood3.61 ± 0.701.40 ± 0.240.56 ± 0.090.14 ± 0.070.04 ± 0.01
    Liver1.25 ± 0.200.55 ± 0.080.27 ± 0.040.09 ± 0.030.05 ± 0.01
    Kidney2.52 ± 0.401.01 ± 0.110.56 ± 0.080.18 ± 0.210.04 ± 0.01
    Intestine1.90 ± 0.200.93 ± 0.120.71 ± 0.150.25 ± 0.090.10 ± 0.06
    Stomach39.25 ± 10.2720.91 ± 1.0020.06 ± 7.941.12 ± 0.530.39 ± 0.20
    Spleen1.79 ± 0.450.72 ± 0.100.32 ± 0.050.08 ± 0.030.04 ± 0.02
    Lung1.89 ± 0.470.79 ± 0.140.32 ± 0.080.09 ± 0.040.04 ± 0.01
    Muscle0.81 ± 0.110.70 ± 0.490.25 ± 0.100.08 ± 0.070.02 ± 0.01
    Bone1.49 ± 0.220.63 ± 0.120.38 ± 0.210.06 ± 0.030.03 ± 0.02
    Tumor (MCF3B)16.73 ± 3.2613.02 ± 4.657.17 ± 1.811.78 ± 0.710.22 ± 0.13
    Tumor (MCF7)2.45 ± 0.800.69 ± 0.170.37 ± 0.030.10 ± 0.080.02 ± 0.01
    T/B ratio4.84 ± 1.529.54 ± 4.1612.93 ± 2.5312.97 ± 1.094.75 ± 2.12
    T/K ratio6.90 ± 2.1712.87 ± 4.2213.06 ± 3.9915.29 ± 6.025.67 ± 2.15
    • Data are mean ± SD of %ID/g and its tumor (MCF3B)-to-blood (T/B) or tumor (MCF3B)-to-kidney (T/K) ratio in 4–5 mice.

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Journal of Nuclear Medicine
Vol. 41, Issue 11
November 1, 2000
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Establishment and Characterization of a Breast Cancer Cell Line Expressing Na+/I− Symporters for Radioiodide Concentrator Gene Therapy
Yuji Nakamoto, Tsuneo Saga, Takashi Misaki, Hisataka Kobayashi, Noriko Sato, Takayoshi Ishimori, Shinji Kosugi, Harumi Sakahara, Junji Konishi
Journal of Nuclear Medicine Nov 2000, 41 (11) 1898-1904;

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Establishment and Characterization of a Breast Cancer Cell Line Expressing Na+/I− Symporters for Radioiodide Concentrator Gene Therapy
Yuji Nakamoto, Tsuneo Saga, Takashi Misaki, Hisataka Kobayashi, Noriko Sato, Takayoshi Ishimori, Shinji Kosugi, Harumi Sakahara, Junji Konishi
Journal of Nuclear Medicine Nov 2000, 41 (11) 1898-1904;
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  • Transfection of the Human Sodium/Iodide Symporter (NIS) Gene with Liposomes and the Expression of the NIS Protein in Human Lung A549 Cancer Cells
  • Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV({Delta}51)-NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide symporter gene
  • Enhanced Expression of Adenovirus-Mediated Sodium Iodide Symporter Gene in MCF-7 Breast Cancer Cells with Retinoic Acid Treatment
  • A perspective view of sodium iodide symporter research and its clinical implications.
  • Development of a Sodium/Iodide Symporter (NIS)-Transgenic Mouse for Imaging of Cardiomyocyte-Specific Reporter Gene Expression
  • In vivo Radioiodide Imaging and Treatment of Breast Cancer Xenografts after MUC1-Driven Expression of the Sodium Iodide Symporter
  • Long-Term Radioiodine Retention and Regression of Liver Cancer after Sodium Iodide Symporter Gene Transfer in Wistar Rats
  • Establishment of a Human Hepatocellular Carcinoma Cell Line Highly Expressing Sodium Iodide Symporter for Radionuclide Gene Therapy
  • Iodide Kinetics and Dosimetry In Vivo After Transfer of the Human Sodium Iodide Symporter Gene in Rat Thyroid Carcinoma Cells
  • Kinetics of Perrhenate Uptake and Comparative Biodistribution of Perrhenate, Pertechnetate, and Iodide by NaI Symporter-Expressing Tissues In Vivo
  • Systemic Retinoic Acid Treatment Induces Sodium/Iodide Symporter Expression and Radioiodide Uptake in Mouse Breast Cancer Models
  • In Vitro Cytotoxicity of 211At-Astatide and 131I-Iodide to Glioma Tumor Cells Expressing the Sodium/Iodide Symporter
  • Radioiodide Treatment after Sodium Iodide Symporter Gene Transfer Is a Highly Effective Therapy in Neuroendocrine Tumor Cells
  • Sodium Iodide Symporter: Its Role in Nuclear Medicine
  • The Endogenous Mammary Gland Na+/I- Symporter May Mediate Effective Radioiodide Therapy in Breast Cancer
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