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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

View larger version (16K): [in this window] [in a new window]   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.

View larger version (13K): [in this window] [in a new window]   FIGURE 2. Iodide uptake plotted against Na+ concentration (A), I– concentration (B), and cell numbers (C).

View larger version (13K): [in this window] [in a new window]   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.

View larger version (14K): [in this window] [in a new window]   FIGURE 4. Tumor-to-normal tissue ratios. High ratios were obtained as early as 1 h after injection, except in stomach.

View larger version (14K): [in this window] [in a new window]   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.

View larger version (63K): [in this window] [in a new window]   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).

View larger version (12K): [in this window] [in a new window]   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.