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OtherBasic Science Investigations

Evaluation of a Transgenic Mouse Model for Anti-Human CEA Radioimmunotherapeutics

Robert W. Wilkinson, Elizabeth L. Ross, David Ellison, Wolfgang Zimmermann, David Snary and Stephen J. Mather
Journal of Nuclear Medicine October 2002, 43 (10) 1368-1376;
Robert W. Wilkinson
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Elizabeth L. Ross
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David Ellison
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Wolfgang Zimmermann
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David Snary
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Stephen J. Mather
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  • FIGURE 1.
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    FIGURE 1.

    mPR1A3 binding to human CEA. (A) mPR1A3 binding to cell-surface CEA was determined by flow cytometry. C15 cells were stained with either mPR1A3, anti-CEA polyclonal serum, or IC mAb. (B) mPR1A3 binding to soluble CEA was determined by ELISA.

  • FIGURE 2.
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    FIGURE 2.

    Human CEA expression in CEA.Tg mouse, shown by immunoperoxidase staining of gastrointestinal tract. Anti-CEA antisera stained CEA.Tg colon (A) and wild-type colon (B); hPR1A3 stained CEA.Tg colon (C) and wild-type colon (D); and hPR1A3 stained CEA.Tg cecum (E) and wild-type cecum (F).

  • FIGURE 3.
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    FIGURE 3.

    mPR1A3 binding to intestine of CEA.Tg (Tg) mice and wild-type (Wt) littermates. Mean %ID per organ and SEs are shown. Results are representative of 3 separate experiments. *Statistically significant difference (P < 0.05) between uptake of mPR1A3 in transgenic and wild-type animals. ▵Statistically significant difference (P < 0.05) between mPR1A3 and IC uptake in transgenic animals.

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    FIGURE 4.

    Comparisons of mPR1A3 uptake in tumor-bearing CEA.Tg and nude mice, including %ID in intestines of tumor-bearing mice (A) and %ID/g in tumor from same mice (B). Groups contained 4 mice, and SEs for mean %ID values are shown. Results are representative of 2 separate experiments.

Tables

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    TABLE 1

    Biodistribution of 125I-Radiolabeled mAbs in Wild-Type C57BL/6 Mice

    TissuemPR1A3IC
    4 h24 h48 h4 h24 h48 h
    %ID per organ*
     Spleen0.41 ± 0.070.28 ± 0.040.22 ± 0.020.38 ± 0.110.30 ± 0.020.25 ± 0.03
     Kidney1.43 ± 0.241.05 ± 0.090.81 ± 0.071.43 ± 0.181.08 ± 0.021.00 ± 0.13
     Intestines5.44 ± 0.513.11 ± 0.362.54 ± 0.144.88 ± 0.803.18 ± 0.052.91 ± 0.29
     Stomach1.37 ± 0.240.42 ± 0.060.36 ± 0.041.01 ± 0.260.59 ± 0.160.43 ± 0.04
     Liver6.98 ± 0.964.80 ± 0.693.81 ± 0.406.19 ± 0.724.45 ± 0.344.13 ± 0.54
    %ID/g*
     Blood24.73 ± 5.0314.55 ± 1.3313.21 ± 1.3826.43 ± 6.4915.16 ± 2.1414.41 ± 2.26
     Muscle1.40 ± 1.210.93 ± 0.220.94 ± 0.120.65 ± 0.130.74 ± 0.471.17 ± 0.26
     Bone1.76 ± 0.371.49 ± 0.791.26 ± 0.071.30 ± 0.221.41 ± 0.251.38 ± 0.17
    • ↵* Mean (n = 4) ± SD.

    • There were no statistically significant differences in tissue distribution of the 2 antibodies.

    • View popup
    TABLE 2

    Biodistribution of 125I-Radiolabeled mAbs in CEA Transgenic Mice

    TissuemPR1A3IC
    4 h24 h48 h4 h24 h48 h
    %ID per organ*
     Spleen0.45 ± 0.080.30 ± 0.050.18 ± 0.030.42 ± 0.050.36 ± 0.040.28 ± 0.02
     Kidney1.46 ± 0.310.84 ± 0.10†0.75 ± 0.131.59 ± 0.151.23 ± 0.101.06 ± 0.20
     Intestines8.31 ± 1.31†10.27 ± 0.86†8.49 ± 0.68†5.37 ± 0.243.74 ± 0.183.30 ± 0.33
     Stomach0.88 ± 0.150.90 ± 0.12†0.72 ± 0.08†0.77 ± 0.080.63 ± 0.100.48 ± 0.13
     Liver6.99 ± 0.913.97 ± 0.22†2.81 ± 0.337.69 ± 0.775.79 ± 0.344.51 ± 0.49
    %ID/g*
     Blood25.41 ± 2.6617.33 ± 1.95†11.80 ± 2.8626.66 ± 3.4721.31 ± 2.0016.20 ± 1.70
     Muscle1.03 ± 0.121.16 ± 0.160.93 ± 0.050.81 ± 0.151.22 ± 0.081.13 ± 0.12
     Bone1.67 ± 0.291.50 ± 0.06†1.20 ± 0.191.66 ± 0.031.71 ± 0.101.49 ± 0.26
    • ↵* Mean (n = 4) ± SD.

    • ↵† Statistically significant difference (P < 0.05) between mPR1A3 and IC antibody.

    • View popup
    TABLE 3

    Biodistribution of 125I-Radiolabeled mAbs in CEA Transgenic Mice Bearing CEA-Transfected Tumors

    TissuemPR1A3IC
    4 h24 h48 h4 h24 h48 h
    %ID per organ*
     Spleen0.43 ± 0.080.21 ± 0.030.16 ± 0.060.55 ± 0.150.61 ± 0.730.29 ± 0.14
     Kidney1.42 ± 0.300.74 ± 0.150.58 ± 0.181.78 ± 0.261.15 ± 0.441.05 ± 0.38
     Intestines8.22 ± 1.567.74 ± 2.11†6.59 ± 1.57†6.04 ± 1.253.70 ± 1.272.99 ± 1.19
     Stomach1.34 ± 0.240.80 ± 0.170.54 ± 0.072.28 ± 0.641.16 ± 0.350.92 ± 0.31
     Liver9.49 ± 0.924.33 ± 2.212.55 ± 0.728.97 ± 1.594.54 ± 1.664.29 ± 1.85
    %ID/g*
     Blood28.87 ± 5.5712.07 ± 2.2510.25 ± 2.0434.82 ± 7.1321.04 ± 11.4519.80 ± 6.36
     Muscle0.75 ± 0.110.92 ± 0.180.82 ± 0.251.11 ± 0.261.31 ± 0.301.67 ± 0.91
     Bone1.84 ± 0.141.56 ± 0.201.12 ± 0.262.47 ± 0.522.04 ± 0.552.22 ± 0.89
     Tumor35.26 ± 7.92†50.43 ± 11.80†46.60 ± 9.39†12.07 ± 2.678.89 ± 4.6710.42 ± 3.19
    • ↵* Mean (n = 4) ± SD.

    • ↵† Statistically significant difference (P < 0.05) between mPR1A3 and IC antibody.

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Journal of Nuclear Medicine: 43 (10)
Journal of Nuclear Medicine
Vol. 43, Issue 10
October 1, 2002
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Evaluation of a Transgenic Mouse Model for Anti-Human CEA Radioimmunotherapeutics
Robert W. Wilkinson, Elizabeth L. Ross, David Ellison, Wolfgang Zimmermann, David Snary, Stephen J. Mather
Journal of Nuclear Medicine Oct 2002, 43 (10) 1368-1376;

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Evaluation of a Transgenic Mouse Model for Anti-Human CEA Radioimmunotherapeutics
Robert W. Wilkinson, Elizabeth L. Ross, David Ellison, Wolfgang Zimmermann, David Snary, Stephen J. Mather
Journal of Nuclear Medicine Oct 2002, 43 (10) 1368-1376;
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