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OtherBasic Science Investigations

MicroPET Imaging of Gene Transfer with a Somatostatin Receptor–Based Reporter Gene and 94mTc-Demotate 1

Buck E. Rogers, Jesse J. Parry, Rebecca Andrews, Paul Cordopatis, Berthold A. Nock and Theodosia Maina
Journal of Nuclear Medicine November 2005, 46 (11) 1889-1897;
Buck E. Rogers
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Jesse J. Parry
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Rebecca Andrews
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Paul Cordopatis
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Berthold A. Nock
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Theodosia Maina
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  • FIGURE 1.
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    FIGURE 1.

    Structure of Demotate 1.

  • FIGURE 2.
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    FIGURE 2.

    Representative plot of 94mTc-Demotate 1–Demotate 1 saturation binding curve (A) and Scatchard transformation (B) for membrane preparations from A-427 cells infected with AdHASSTR2 at 10 pfu per cell. It should be noted that 94mTc-Demotate 1 concentrations included unlabeled Demotate 1 and that saturation binding curve represented specific binding (nonspecifically bound subtracted from total bound). Each data point represents mean ± SEM of triplicate measurements.

  • FIGURE 3.
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    FIGURE 3.

    Specific internalization at 37°C of 94mTc-Demotate 1 into A-427 cells infected with AdHASSTR2 at 10 pfu per cell. 94mTc-Demotate 1 (1 nmol/L) was incubated with cells for various times in presence or absence of inhibitor. Cells were acid washed to remove surface-bound radioactivity and then were harvested to determine internalized radioactivity. Specific internalized radioactivity (internalized with inhibitor subtracted from internalized without inhibitor) (▪) and specific surface-bound radioactivity (surface bound with inhibitor subtracted from surface bound without inhibitor) (•) are shown. Data for each time point are presented as mean ± SEM of 2–5 experiments each performed in triplicate.

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    FIGURE 4.

    Biodistribution of 94mTc-Demotate 1 in mice bearing A-427 tumor xenografts. Tumors were injected directly with either AdHASSTR2 or AdGRPR as control, and 94mTc-Demotate 1 was injected via tail vein 2 d later. Mice were sacrificed 1 h (▪) and 2 h (□) later (n = 6 for each group). Data are presented as mean ± SEM %ID/g for each type of tissue (A) and as ratio of AdHASSTR2-injected tumor uptake to tissue uptake at both time points (B).

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    FIGURE 5.

    (A and B) Coronal (A) and transaxial (B) microPET projection images of A-427 tumor–bearing mice at 1 h after injection of 94mTc-Demotate 1. Mice carried axillary tumors in which left tumor was injected directly with AdHASSTR2 and right tumor was injected with AdGRPR. Coronal image shows uptake of 94mTc-Demotate 1 in AdHASSTR2-injected tumor and clearance through kidneys and bladder but background uptake in AdGRPR-injected tumor. (C) SUVs obtained from microPET images for AdGRPR-injected tumors, AdHASSTR2-injected tumors, and kidneys in 3 mice at 1 h (▪) and 2 h (□). (D) Ratios of uptake in AdHASSTR2-injected tumors to that in AdGRPR-injected tumors and of uptake in AdHASSTR2-injected tumors to that in kidneys, as determined by SUV analysis (red bars; n = 3) and biodistribution analysis (blue bars; n = 11 for 1 h and n = 6 for 2 h). Data in C and D are presented as mean ± SEM.

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    TABLE 1

    Biodistribution (n = 5) of 94mTc-Demotate 1 in Mice Bearing A-427 Tumor Xenografts Directly Injected with AdHASSTR2 or AdGRPR*

    TissueMean ± SEM %ID/g for:
    Unblocked samplesBlocked samples
    Blood0.37 ± 0.050.41 ± 0.09
    Lungs1.16 ± 0.270.59 ± 0.08
    Liver1.37 ± 0.230.64 ± 0.06†
    Spleen0.56 ± 0.160.24 ± 0.02
    Kidneys9.43 ± 1.135.90 ± 0.97†
    Muscle0.27 ± 0.080.33 ± 0.09
    Bone1.09 ± 0.340.30 ± 0.04
    Pancreas21.31 ± 1.530.22 ± 0.03†
    AdGRPR-injected tumors0.82 ± 0.061.33 ± 0.18
    AdHASSTR2-injected tumors5.39 ± 0.841.56 ± 0.26†
    • ↵* Mice were sacrificed 1 h after intravenous injection of 94mTc-Demotate 1 with or without coinjection of 50 μg of unlabeled Demotate 1 as blocking agent.

    • ↵† Value for blocked sample was significantly lower (P < 0.05) than value for unblocked sample.

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Journal of Nuclear Medicine: 46 (11)
Journal of Nuclear Medicine
Vol. 46, Issue 11
November 1, 2005
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MicroPET Imaging of Gene Transfer with a Somatostatin Receptor–Based Reporter Gene and 94mTc-Demotate 1
Buck E. Rogers, Jesse J. Parry, Rebecca Andrews, Paul Cordopatis, Berthold A. Nock, Theodosia Maina
Journal of Nuclear Medicine Nov 2005, 46 (11) 1889-1897;

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MicroPET Imaging of Gene Transfer with a Somatostatin Receptor–Based Reporter Gene and 94mTc-Demotate 1
Buck E. Rogers, Jesse J. Parry, Rebecca Andrews, Paul Cordopatis, Berthold A. Nock, Theodosia Maina
Journal of Nuclear Medicine Nov 2005, 46 (11) 1889-1897;
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