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Research ArticleBasic Science Investigations

Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET

Ganesan Vaidyanathan, Darryl McDougald, Jaeyeon Choi, Eftychia Koumarianou, Douglas Weitzel, Takuya Osada, H. Kim Lyerly and Michael R. Zalutsky
Journal of Nuclear Medicine June 2016, 57 (6) 967-973; DOI: https://doi.org/10.2967/jnumed.115.171306
Ganesan Vaidyanathan
1Department of Radiology, Duke University Medical Center, Durham, North Carolina
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Darryl McDougald
1Department of Radiology, Duke University Medical Center, Durham, North Carolina
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Jaeyeon Choi
1Department of Radiology, Duke University Medical Center, Durham, North Carolina
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Eftychia Koumarianou
1Department of Radiology, Duke University Medical Center, Durham, North Carolina
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Douglas Weitzel
2Department of Radiation Oncology and Cancer Biology, Duke University Medical Center, Durham, North Carolina; and
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Takuya Osada
3Department of Surgery, Duke University Medical Center, Durham, North Carolina
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H. Kim Lyerly
3Department of Surgery, Duke University Medical Center, Durham, North Carolina
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Michael R. Zalutsky
1Department of Radiology, Duke University Medical Center, Durham, North Carolina
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  • FIGURE 1.
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    FIGURE 1.

    Structures of *I-SGMIB and 18F-SFB and scheme for labeling 5F7 Nanobody using 18F-RL-I.

  • FIGURE 2.
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    FIGURE 2.

    Paired-label internalization of 125I-SGMIB-5F7 (blue bars) versus 18F-RL-I-5F7 (magenta bars) (A) and 125I-SGMIB-5F7 (blue bars) versus 18F-SFB-5F7 (green bars) (B) in BT-471M1 breast cancer cells in vitro. (C) Ratio of 18F to 125I obtained from 2 experiments.

  • FIGURE 3.
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    FIGURE 3.

    18F-to-125I ratio in tumor from paired-label biodistribution of 18F-RL-I5F7 and 125I-SGMIB-5F7 and 18F-SFB-5F7 and 125I-SGMIB-5F7 in severe combined immunodeficiency mice bearing BT474M1 xenografts. Green bars = 18F-RL-I-5F7; magenta bars = 18F-SFB-5F7.

  • FIGURE 4.
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    FIGURE 4.

    Tumor-to-tissue ratios for selected tissues obtained from biodistribution of 18F-RL-I-5F7 (A) and 18F-SFB-5F7 (B).

  • FIGURE 5.
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    FIGURE 5.

    PET/CT images of mice bearing BT474M1 xenografts after injection of 18F-RL-I-5F7. Images were obtained at 1 and 2 h without and at 1 h with blocking of HER2 receptors by preadministration of trastuzumab.

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    TABLE 1

    Paired-Label Biodistribution of 18F-RL-I-5F7 and 125I-SGMIB-5F7 in Severe Combined Immunodeficiency Mice Bearing BT474M1 Xenografts

    %ID/g*
    1 h2 h
    Tissue125I-SGMIB18F-RL-I-5F7125I-SGMIB18F-RL-I-5F7
    Liver3.27 ± 0.613.42 ± 0.57†3.12 ± 0.943.17 ± 1.13†
    Spleen2.01 ± 0.621.63 ± 0.511.85 ± 0.491.31 ± 0.40
    Lung10.47 ± 2.279.07 ± 1.06†8.03 ± 0.836.63 ± 1.46†
    Heart1.43 ± 0.471.30 ± 0.53†0.62 ± 0.150.54 ± 0.14†
    Kidney122.68 ± 18.03139.45 ± 20.5496.92 ± 30.55105.02 ± 39.52†
    Stomach1.91 ± 0.771.97 ± 0.78†0.59 ± 0.280.54 ± 0.23†
    Small intestine1.71 ± 0.522.10 ± 0.590.94 ± 0.301.28 ± 0.42
    Large intestine1.36 ± 0.311.68 ± 0.371.89 ± 1.302.47 ± 1.63
    Muscle1.16 ± 0.481.27 ± 0.500.91 ± 0.301.10 ± 0.38†
    Blood1.75 ± 0.841.95 ± 0.870.65 ± 0.410.83 ± 0.43
    Bone0.76 ± 0.370.97 ± 0.310.78 ± 0.231.13 ± 0.28
    Brain0.10 ± 0.040.11 ± 0.040.07 ± 0.010.07 ± 0.02†
    Tumor26.36 ± 3.1228.97 ± 3.8832.52 ± 12.1136.28 ± 14.10
    • ↵* Mean ± SD (n = 5).

    • ↵† Difference in uptake not statistically significant.

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    TABLE 2

    Paired Label Biodistribution of 18F-SFB-5F7 and 125I-SGMIB-5F7 in Severe Combined Immunodeficiency Mice Bearing BT474M1 Xenografts

    %ID/g*
    1 h2 h
    Tissue125I-SGMIB18F-SFB125I-SGMIB18F-SFB
    Liver2.02 ± 0.470.95 ± 0.212.18 ± 0.550.68 ± 0.13
    Spleen1.08 ± 0.330.67 ± 0.371.28 ± 0.220.52 ± 0.13
    Lung2.96 ± 0.392.31 ± 0.402.56 ± 0.702.00 ± 0.38†
    Heart0.76 ± 0.200.62 ± 0.150.62 ± 0.130.54 ± 0.15†
    Kidney102.50 ± 26.353.90 ± 1.1393.00 ± 18.822.90 ± 0.77
    Stomach1.32 ± 1.171.43 ± 1.69†1.98 ± 1.123.21 ± 4.62†
    Small intestine1.17 ± 0.550.69 ± 0.331.32 ± 0.460.59 ± 0.19
    Large intestine1.18 ± 0.470.69 ± 0.503.86 ± 5.471.22 ± 1.66†
    Muscle1.14 ± 0.271.16 ± 0.37†1.21 ± 0.891.43 ± 1.20†
    Blood0.96 ± 0.261.25 ± 0.290.67 ± 0.511.44 ± 0.88
    Bone0.88 ± 0.360.97 ± 0.55†0.51 ± 0.090.54 ± 0.08†
    Brain0.07 ± 0.020.09 ± 0.020.08 ± 0.050.12 ± 0.06
    Tumor27.88 ± 8.0823.94 ± 7.0033.59 ± 6.2429.59 ± 5.10
    • ↵* Mean ± SD (n = 5).

    • ↵† Difference in uptake not statistically significant.

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    TABLE 3

    Tumor SUV and %ID/g from Small-Animal PET/CT Imaging of Severe Combined Immunodeficiency Mice Bearing BT474M1 Xenografts after Injection of 18F-RL-I-5F7

    1 h2 h
    Mouse no.SUV%ID/gSUV%ID/g
    Unblocked
     1*4.2 ± 0.722.4 ± 3.84.3 ± 0.823.0 ± 4.2
     2*3.3 ± 0.417.8 ± 2.13.6 ± 0.719.4 ± 4.1
     3†4.9 ± 0.726.4 ± 3.94.9 ± 0.826.2 ± 4.2
     4†4.4 ± 0.624.9 ± 3.34.6 ± 0.726.1 ± 3.7
    Blocked
     1*0.4 ± 0.12.1 ± 0.1NDND
     2*0.4 ± 0.12.1 ± 0.8NDND
     3†0.3 ± 0.11.3 ± 0.5NDND
     4†0.2 ± 0.11.0 ± 0.5NDND
    • ↵* Batch1.

    • ↵† Batch2.

    • ND = not determined.

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Journal of Nuclear Medicine: 57 (6)
Journal of Nuclear Medicine
Vol. 57, Issue 6
June 1, 2016
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Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET
Ganesan Vaidyanathan, Darryl McDougald, Jaeyeon Choi, Eftychia Koumarianou, Douglas Weitzel, Takuya Osada, H. Kim Lyerly, Michael R. Zalutsky
Journal of Nuclear Medicine Jun 2016, 57 (6) 967-973; DOI: 10.2967/jnumed.115.171306

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Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET
Ganesan Vaidyanathan, Darryl McDougald, Jaeyeon Choi, Eftychia Koumarianou, Douglas Weitzel, Takuya Osada, H. Kim Lyerly, Michael R. Zalutsky
Journal of Nuclear Medicine Jun 2016, 57 (6) 967-973; DOI: 10.2967/jnumed.115.171306
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Keywords

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