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Article

Preclinical evaluation of 99mTc direct labeling ZHER2:V2 for HER2 positive tumors imaging

  • Authors:
    • Yang Yang
    • Xinming Zhao
    • Yu Xing
    • Tianying Yu
    • Jingmian Zhang
    • Jianfang Wang
  • View Affiliations / Copyright

    Affiliations: Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University and The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
  • Pages: 5361-5366
    |
    Published online on: August 8, 2018
       https://doi.org/10.3892/ol.2018.9279
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Abstract

The present study aimed to label ZHER2:V2 with technetium‑99m (99mTc) using a simple method and to evaluate its clinical potential as a diagnostic probe for human epidermal growth factor receptor type 2 (HER2)‑positive tumors. The ZHER2:V2 (Affibody molecule of ZHER2:2395‑C, which is based on the ZHER2:342 binding sequence with C‑terminal engineered cysteine) with C‑terminal chelating sequence GGGC was designed and labeled with 99mTc. The 99mTc‑ZHER2:V2 labeling efficiency was analyzed. The cellular uptake, retention and binding affinity, and the stability of the probe were examined in vitro. 99mTc‑ZHER2:V2 biodistribution analysis and imaging were performed in BALB/c nude mice bearing SKOV3 (HER2‑overexpression) xenografts. Furthermore, imaging of the probe was performed in MCF‑7 (HER2 low‑expression) xenografts. The 99mTc‑ZHER2:V2 labeling efficiency was identified as 98.99±0.99% (n=6), and was stable in physiological saline and fresh human serum at 37˚C in vitro. The cellular uptake peak of SKOV3 cells at 24 h was 6.15±0.18%, the cellular retention ratio of the probe was 48.58±4.52% at 6 h following interrupted incubation, and ~70% of 99mTc‑ZHER2:V2 was membrane bound following 24 h. 99mTc‑ZHER2:V2 was blocked by excess amounts of unlabeled ZHER2:V2 in SKOV3 cells. 99mTc‑ZHER2:V2 exhibited high distribution (10.07% ID/g) in SKOV3 xenografts at 6 h following injection. The single photon emission computed tomography (SPECT) imaging revealed clear localization of 99mTc‑ZHER2:V2 in the SKOV3 xenografts at 4 h. However, there was low uptake in MCF‑7 tumors on the SPECT images. The SKOV3 xenograft imaging could be blocked by excess amounts unlabelled ZHER2:V2. 99mTc‑ZHER2:V2 is an easy and quick labeling method, with high labeling yields, and radiochemical purity. 99mTc‑ZHER2:V2 is a promising probe for the diagnosis of HER2‑overexpression tumors and the monitoring of therapy response.
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Copy and paste a formatted citation
Spandidos Publications style
Yang Y, Zhao X, Xing Y, Yu T, Zhang J and Wang J: Preclinical evaluation of 99mTc direct labeling ZHER2:V2 for HER2 positive tumors imaging. Oncol Lett 16: 5361-5366, 2018.
APA
Yang, Y., Zhao, X., Xing, Y., Yu, T., Zhang, J., & Wang, J. (2018). Preclinical evaluation of 99mTc direct labeling ZHER2:V2 for HER2 positive tumors imaging. Oncology Letters, 16, 5361-5366. https://doi.org/10.3892/ol.2018.9279
MLA
Yang, Y., Zhao, X., Xing, Y., Yu, T., Zhang, J., Wang, J."Preclinical evaluation of 99mTc direct labeling ZHER2:V2 for HER2 positive tumors imaging". Oncology Letters 16.4 (2018): 5361-5366.
Chicago
Yang, Y., Zhao, X., Xing, Y., Yu, T., Zhang, J., Wang, J."Preclinical evaluation of 99mTc direct labeling ZHER2:V2 for HER2 positive tumors imaging". Oncology Letters 16, no. 4 (2018): 5361-5366. https://doi.org/10.3892/ol.2018.9279
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Y, Zhao X, Xing Y, Yu T, Zhang J and Wang J: Preclinical evaluation of 99mTc direct labeling ZHER2:V2 for HER2 positive tumors imaging. Oncol Lett 16: 5361-5366, 2018.
APA
Yang, Y., Zhao, X., Xing, Y., Yu, T., Zhang, J., & Wang, J. (2018). Preclinical evaluation of 99mTc direct labeling ZHER2:V2 for HER2 positive tumors imaging. Oncology Letters, 16, 5361-5366. https://doi.org/10.3892/ol.2018.9279
MLA
Yang, Y., Zhao, X., Xing, Y., Yu, T., Zhang, J., Wang, J."Preclinical evaluation of 99mTc direct labeling ZHER2:V2 for HER2 positive tumors imaging". Oncology Letters 16.4 (2018): 5361-5366.
Chicago
Yang, Y., Zhao, X., Xing, Y., Yu, T., Zhang, J., Wang, J."Preclinical evaluation of 99mTc direct labeling ZHER2:V2 for HER2 positive tumors imaging". Oncology Letters 16, no. 4 (2018): 5361-5366. https://doi.org/10.3892/ol.2018.9279
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