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Transfer of the Human NaI Symporter Gene Enhances Iodide Uptake in Hepatoma Cells

Department of Nuclear Medicine, University of Heidelberg, Heidelberg; and Clinical Cooperation Units of Nuclear Medicine and Radiation Therapy, German Cancer Research Center, Heidelberg, Germany

View larger version (7K): [in a new window]   FIGURE 1. Structure of recombinant retroviral vector based on Moloney murine leukemia virus. This vector is designed to transfer human hNIS and hygromycin resistance (hyg) activity by use of internal ribosomal entry site (IRES) from encephalomyocarditis virus. Synthetic intron (IVS) is inserted to stabilize mRNA. Expression of genes is regulated by elongation factor 1 gene (EF1a) promoter. LTR = long terminal repeat.

View larger version (65K): [in a new window]   FIGURE 2. Iodide uptake in FRTL5 cells, wild-type Morris hepatoma cells, and hNIS-expressing Morris hepatoma cells after 4 h incubation with Na125I. Data are mean values and SD (n = 3).

View larger version (19K): [in a new window]   FIGURE 3. Time dependence of 125I- uptake in wild-type Morris hepatoma cells and in hNIS-expressing cell line hNIShyg10. Data are mean values and SD (n = 3).

View larger version (49K): [in a new window]   FIGURE 4. Effect of DIDS, FCCP, and sodium perchlorate on 125I- uptake in hNIShyg10 cell line after 1 h incubation. Data are mean values and SD (n = 3).

View larger version (20K): [in a new window]   FIGURE 5. Iodide efflux from hNIShyg10 cells after 1 h incubation with Na125I with and without 300 µmol/L DIDS. Data are mean values and SD (n = 3).

View larger version (44K): [in a new window]   FIGURE 6. Scintigraphic images of tumor-bearing male young adult ACI rat with subcutaneously transplanted hNIS-expressing (right thigh) or wild-type Morris hepatoma cells (left thigh) at 30 min (A) and at 1 h (B), 2 h (C), and 4 h (D) after injection of 131I-.

View larger version (20K): [in a new window]   FIGURE 7. 131I- uptake (impulses [Imp]/pixel) in hNIS-expressing and wild-type Morris hepatomas at different times after radiotracer application in rats. Data are mean values and SD (n = 3).