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Research ArticleOncology

Radioiodinated Small-Molecule Tyrosine Kinase Inhibitor for HER2-Selective SPECT Imaging

Longguang Tang, Chenyu Peng, Bowen Tang, Zijing Li, Xiangyu Wang, Jindian Li, Fei Gao, Lumei Huang, Duo Xu, Pu Zhang, Rongqiang Zhuang, Xinhui Su, Xiaoyuan Chen and Xianzhong Zhang
Journal of Nuclear Medicine September 2018, 59 (9) 1386-1391; DOI: https://doi.org/10.2967/jnumed.117.205088
Longguang Tang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
2Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, Maryland
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Chenyu Peng
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Bowen Tang
3School of Pharmaceutical Science, Xiamen University, Xiamen, China; and
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Zijing Li
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Xiangyu Wang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Jindian Li
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Fei Gao
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Lumei Huang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Duo Xu
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Pu Zhang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Rongqiang Zhuang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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Xinhui Su
4Zhongshan Hospital, affiliated with Xiamen University, Xiamen, China
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Xiaoyuan Chen
2Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, Maryland
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Xianzhong Zhang
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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  • FIGURE 1.
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    FIGURE 1.

    Chemical structures of CP724,714 (A), 125I- or 131I-labeled CP724,714 (B), and its analog (C).

  • FIGURE 2.
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    FIGURE 2.

    (A) HER2 and EGFR protein levels in different cells evaluated by Western blot. (B) Binding of 131I-IBA-CP to cells with different levels of HER2 expression (cell line vs. normalized cell-associated radioactivity and effect of preincubation with IBA-CP on binding. Data are mean ± SD (n = 3). (C) Representative results of competition-binding assay using MDA-MB-453 cells. (D) Representative results of saturation assay using MDA-MB-453 cells. NSB = nonspecific binding; SB = specific binding; TB = total binding. ***P < 0.001.

  • FIGURE 3.
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    FIGURE 3.

    (A and B) Representative SPECT/CT images obtained 1, 2, 3, and 4 h after injection of 125I-IBA-CP in mice bearing MDA-MB-453 (A) and MCF-7 (B) tumors (circled). (C and D) Respective tumor-to-muscle ratios obtained from images in A and B. n = 4; error bars correspond to SD.

  • FIGURE 4.
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    FIGURE 4.

    (A) Representative SPECT/CT images obtained 3 h after injection of 125I-IBA-CP in mice bearing MDA-MB-453 tumors (circled) with or without blocking dose of nonradioactive compound IBA-CP or erlotinib. (B) Quantification of SPECT imaging results. Data are mean ± SD (n = 4). T/M = tumor-to-muscle ratio. ***P < 0.001.

  • FIGURE 5.
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    FIGURE 5.

    (A) Biodistribution of 131I-IBA-CP in MDA-MB-453 (HER2-positive), MDA-MB-468 (HER2-negative, EGFR-positive), and MCF-7 (HER2-negative) tumor–bearing mice 3 h after injection and in MDA-MB-453 tumor–bearing mice coinjected with nonradioactive compound IBA-CP or erlotinib as blocking agent 30 min after injection. (B) 131I-IBA-CP tumor uptake from A. (C) 131I-IBA-CP tumor-to-muscle ratio from A. Data are mean ± SD (n = 4). T/M = tumor-to-muscle ratio. ***P < 0.001.

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Journal of Nuclear Medicine: 59 (9)
Journal of Nuclear Medicine
Vol. 59, Issue 9
September 1, 2018
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Radioiodinated Small-Molecule Tyrosine Kinase Inhibitor for HER2-Selective SPECT Imaging
Longguang Tang, Chenyu Peng, Bowen Tang, Zijing Li, Xiangyu Wang, Jindian Li, Fei Gao, Lumei Huang, Duo Xu, Pu Zhang, Rongqiang Zhuang, Xinhui Su, Xiaoyuan Chen, Xianzhong Zhang
Journal of Nuclear Medicine Sep 2018, 59 (9) 1386-1391; DOI: 10.2967/jnumed.117.205088

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Radioiodinated Small-Molecule Tyrosine Kinase Inhibitor for HER2-Selective SPECT Imaging
Longguang Tang, Chenyu Peng, Bowen Tang, Zijing Li, Xiangyu Wang, Jindian Li, Fei Gao, Lumei Huang, Duo Xu, Pu Zhang, Rongqiang Zhuang, Xinhui Su, Xiaoyuan Chen, Xianzhong Zhang
Journal of Nuclear Medicine Sep 2018, 59 (9) 1386-1391; DOI: 10.2967/jnumed.117.205088
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Keywords

  • HER2
  • tyrosine kinase inhibitor
  • radioiodinated IBA-CP
  • breast cancer
  • small-animal SPECT
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