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
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  • Published online on: August 8, 2018     https://doi.org/10.3892/ol.2018.9279
  • Pages: 5361-5366
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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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October-2018
Volume 16 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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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