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Research ArticleBasic Science Investigations

Improved Tumor Targeting of Anti-HER2 Nanobody Through N-Succinimidyl 4-Guanidinomethyl-3-Iodobenzoate Radiolabeling

Marek Pruszynski, Eftychia Koumarianou, Ganesan Vaidyanathan, Hilde Revets, Nick Devoogdt, Tony Lahoutte, H. Kim Lyerly and Michael R. Zalutsky
Journal of Nuclear Medicine April 2014, 55 (4) 650-656; DOI: https://doi.org/10.2967/jnumed.113.127100
Marek Pruszynski
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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Ganesan Vaidyanathan
1Department of Radiology, Duke University Medical Center, Durham, North Carolina
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Hilde Revets
2Ablynx N.V., Ghent, Belgium
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Nick Devoogdt
3In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Brussels, Belgium
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Tony Lahoutte
3In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Brussels, Belgium
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H. Kim Lyerly
4Department of Surgery, Duke University Medical Center, Durham, North Carolina; and
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Michael R. Zalutsky
1Department of Radiology, Duke University Medical Center, Durham, North Carolina
5Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
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  • FIGURE 1.
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    FIGURE 1.

    Cellular processing of radioiodinated Nanobody in BT474M1 cells. (A and B) 125I-Nanobody (○) vs. 131I-SGMIB-Nanobody (●): internalized (A) and supernatant (B). (C and D) 131I-IB-Mal-d-GEEEK-Nanobody (□) vs. 125I-SGMIB-Nanobody (▪): internalized (C) and supernatant (D).

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    FIGURE 2.

    Uptake of radioiodine in athymic mice with BT474M1 xenografts. (A and B) 125I-Nanobody (hatched) vs. 131I-SGMIB-Nanobody (black): tumor (A) and kidneys (B). (C and D) 131I-IB-Mal-d-GEEEK-Nanobody (white) vs. 125I-SGMIB-Nanobody (black): tumor (C) and kidneys (D). *Difference not significant (P > 0.05).

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    FIGURE 3.

    Tumor–to–normal-tissue ratios in athymic mice bearing subcutaneous BT474M1 xenografts for 131I-IB-Mal-d-GEEEK-Nanobody (○) and 125I-SGMIB-Nanobody (●): liver (A), spleen (B), lungs (C), kidneys (D), heart (E), stomach (F), blood (G), and muscle (H).

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    TABLE 1

    Effect of 10 mg of Trastuzumab on Radioiodinated Nanobody Uptake in BT474M1 Xenografts and Normal Tissues

    Experiment 1Experiment 2
    125I-Nanobody (185 kBq, 0.6 μg)131I-SGMIB-Nanobody (185 kBq, 1.0 μg)125I-SGMIB-Nanobody (93 kBq, 1.6 μg)131I-IB-Mal-d-GEEK-Nanobody (150 kBq, 0.7 μg)
    TissueNot blockedBlockedNot blockedBlockedNot blockedBlockedNot blockedBlocked
    Liver7.76 ± 1.566.28 ± 0.722.65 ± 0.652.45 ± 0.341.95 ± 0.421.72 ± 0.1113.32 ± 1.7512.71 ± 0.76
    Spleen3.90 ± 1.773.32 ± 0.491.13 ± 0.471.03 ± 0.371.09 ± 0.290.92 ± 0.142.68 ± 0.382.99 ± 0.86
    Kidneys26.05 ± 5.8621.54 ± 1.0944.0 ± 12.042.30 ± 4.6634.98 ± 5.5736.89 ± 5.48174.8 ± 28.2197.2 ± 22.4
    Blood10.08 ± 1.476.56 ± 0.65*1.15 ± 0.251.04 ± 0.160.70 ± 0.100.69 ± 0.090.69 ± 0.090.70 ± 0.09
    Tumor6.39 ± 1.972.27 ± 0.22*24.50 ± 9.892.14 ± 0.21*12.57 ± 2.771.26 ± 0.13*6.23 ± 1.320.68 ± 0.06*
    • ↵* Significant blocking effect (P < 0.05).

    • Data are %ID/g (mean ± SD; n = 5).

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Journal of Nuclear Medicine: 55 (4)
Journal of Nuclear Medicine
Vol. 55, Issue 4
April 1, 2014
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Improved Tumor Targeting of Anti-HER2 Nanobody Through N-Succinimidyl 4-Guanidinomethyl-3-Iodobenzoate Radiolabeling
Marek Pruszynski, Eftychia Koumarianou, Ganesan Vaidyanathan, Hilde Revets, Nick Devoogdt, Tony Lahoutte, H. Kim Lyerly, Michael R. Zalutsky
Journal of Nuclear Medicine Apr 2014, 55 (4) 650-656; DOI: 10.2967/jnumed.113.127100

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Improved Tumor Targeting of Anti-HER2 Nanobody Through N-Succinimidyl 4-Guanidinomethyl-3-Iodobenzoate Radiolabeling
Marek Pruszynski, Eftychia Koumarianou, Ganesan Vaidyanathan, Hilde Revets, Nick Devoogdt, Tony Lahoutte, H. Kim Lyerly, Michael R. Zalutsky
Journal of Nuclear Medicine Apr 2014, 55 (4) 650-656; DOI: 10.2967/jnumed.113.127100
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Keywords

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