Research ArticleBasic Science Investigation

Imaging Expression of the Human Somatostatin Receptor Subtype-2 Reporter Gene with 68Ga-DOTATOC

Hanwen Zhang, Maxim A. Moroz, Inna Serganova, Thomas Ku, Ruimin Huang, Jelena Vider, Helmut R. Maecke, Steven M. Larson, Ronald Blasberg and Peter M. Smith-Jones
Journal of Nuclear Medicine January 2011, 52 (1) 123-131; DOI: https://doi.org/10.2967/jnumed.110.079004

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Kinetics of 67Ga-DOTATOC binding to and dissociation from hSSTr2 expressed by transduced cells. Dissociation of ligand–receptor complex was initiated by addition of excess natGa-DOTATOC after 0.25 and 1 h. Results (mean ± SD) are from 2–4 independent studies. Solid line = 37°C; dotted line = 24°C.

  • FIGURE 2.
    FIGURE 2.

    In vitro uptake of 67Ga-DOTATOC by hSSTr2-transduced cells. (A) Accumulation of 67Ga-DOTATOC in WT and hSSTr-transduced cells after 2 h incubation at 37°C. natGa-DOTATOC or somatostatin-14 (1 μM) was used in blocking experiments. (B) Correlation of 67Ga-DOTATOC uptake vs. Bmax for different hSSTr2-transduced cell lines. NCA = no natGa-DOTATOC or somatostatin-14 added.

  • FIGURE 3.
    FIGURE 3.

    Small-animal PET and fluorescence imaging of hSSTr2-transduced xenografts. (A) Optical small-animal PET projection and transaxial images of mouse with 3 transduced xenografts at 2 h after injection of 68Ga-DOTATOC. (B) GFP–fluorescence, small-animal PET projection, and transaxial images of mouse with 2 WT and 2 transduced xenografts at 2 h after injection of 68Ga-DOTATOC. Radioactivity in kidneys and bladder is visualized in projection images. CT = C6-SSTr2; Cw = C6-WT; JT = Jurkat-SSTr2; UT = U87-SSTr2; Uw = U87-WT.

  • FIGURE 4.
    FIGURE 4.

    Small-animal PET tumor uptake of 68Ga-DOTATOC. (A) Uptake (%ID/mL) derived from small-animal PET at 1 and 2 h after injection of 68Ga-DOTATOC. (B) Correlation of uptake values derived from small-animal PET and biodistribution for 68Ga-DOTATOC. CT = C6-SSTr2; Cw = C6-WT; JT = Jurkat-SSTr2; Jw = Jurkat-WT; UT = U87-SSTr2; Uw = U87-WT.

  • FIGURE 5.
    FIGURE 5.

    68Ga-DOTATOC biodistribution studies. (A) Biodistribution of 68Ga-DOTATOC (%ID/g ± SD) in hSSTr2-transduced tumor-bearing nude mice at 2 h after injection. (B) 68Ga-DOTATOC uptake ratios for hSSTr2-transduced xenograft and normal organs. Ad = adrenal; Bl = blood; Bn = bone; CT = C6-SSTr2; Cw = C6-WT; He = heart; JT = Jurkat-SSTr2; Jw = Jurkat-WT; Ki = kidney; Li = liver; Mu = muscle; Pa = pancreas; Pi = pituitary; Si = small intestines; Sp = spleen; St = stomach; UT = U87-SSTr2; Uw = U87-WT.

  • FIGURE 6.
    FIGURE 6.

    Correlation of in vivo tumor uptake of 68Ga-DOTATOC (%ID/g) and in vitro hSSTr2 expression Bmax.

Tables

  • TABLE 1

    Kd and Bmax Values for natGa-DOTATOC Binding to hSSTr2 Expressed by Transduced Cells

    ParameterJurkat-hSSTr2 (n = 4)CHO-hSSTr2 (n = 7)U87-hSSTr2 (n = 3)C6-hSSTr2 (n = 3)
    Bmax (105 sites/cell)0.36 ± 0.043.09 ± 0.402.82 ± 0.3712.5 ± 1.4
    Kd (nM)5.26 ± 2.735.06 ± 0.916.90 ± 1.537.64 ± 1.43
  • TABLE 2

    Effect of SSTr2 Expression on Xenograft Growth in Athymic Mice

    SSTr2 transfected tumors
    Cell lineTime after inoculation (d)WT tumors, mass (mg) ± SDMass (mg) ± SDBmax (sites/cell)P
    C69–1047 ± 156 ± 181,250,0000.54
    C614–1544 ± 4032 ± 131,250,0000.41
    U878–992 ± 6434 ± 28282,0000.022
    Jurkat35630 ± 44223 ± 635,8000.029
  • TABLE 3

    Comparison of Radioligands for Imaging Human SSTr Reporter Gene

    Uptake
    Transduced xenograftLigand% dose/cm3Ratio of transduced to WTRatio of transduced to muscleReferences
    SKOV3111In-DTPA-octreotide32 (4 h)*†38 (4 h)*†30 (4 h)Rogers et al. (14)
    A-42799mTc-P8292.5 (5 h)*†4 (3 h)*†4 (3 h)Zinn et al. (16)
    188Re-P8292.2 (5 h)*†
    SKOV399mTc-P20454.0 (2 h)*†12.2 (5 h)*†NDChaudhuri et al. (38)
    A-42794mTc-demotate 1>5 (2 h)*‡10 (1 h), 20(2 h)Rogers et al. (17)
    HT1080111In-DTPA-octreotide1.7 (24 h)*†14 (24 h)*†42 (24 h)Yang et al. (39)
    MDA-MB-435111In-DTPA-octreotide1.8 (24 h)*†18 (24 h) *†27 (24 h)Singh et al. (40)
    C668Ga-DOTATOC15 (2 h)*‡64 (2 h)*‡∼500 (2 h)Current work

    • ↵* Mouse.

    • ↵† γ-camera values.

    • ↵‡ PET values.

    • ND = not determined.

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