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Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer

Abstract

Purpose

Human epidermal growth factor receptor 2 (HER2) is over-expressed in over 30% of ovarian cancer cases, playing an essential role in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians as a mean to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using 64Cu-labeled pertuzumab for immunoPET imaging.

Methods

HER2 expression and binding were examined in three ovarian cancer cell lines (SKOV3, OVCAR3, Caov3) using in vitro techniques, including western blot and saturation binding assays. PET imaging and biodistribution studies in subcutaneous models of ovarian cancer were performed for non-invasive in vivo evaluation of HER2 expression. Additionally, orthotopic models were employed to further validate the imaging capability of 64Cu-NOTA-pertuzumab.

Results

HER2 expression was highest in SKOV3 cells, while OVCAR3 and Caov3 displayed lower HER2 expression. 64Cu-NOTA-pertuzumab showed high specificity for HER2 (Ka = 3.1 ± 0.6 nM) in SKOV3. In subcutaneous tumors, PET imaging revealed tumor uptake of 41.8 ± 3.8, 10.5 ± 3.9, and 12.1 ± 2.3%ID/g at 48 h post-injection for SKOV3, OVCAR3, and Caov3, respectively (n = 3). In orthotopic models, PET imaging with 64Cu-NOTA-pertuzumab allowed for rapid and clear delineation of both primary and small peritoneal metastases in HER2-expressing ovarian cancer.

Conclusions

64Cu-NOTA-pertuzumab is an effective PET tracer for the non-invasive imaging of HER2 expression in vivo, rendering it a potential tracer for treatment monitoring and improved patient stratification.

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Acknowledgements

This work was supported in part by the University of Wisconsin - Madison, the National Institutes of Health (NIBIB/NCI 1R01CA169365, 1R01EB021336, P30CA014520, T32CA009206, T32GM008505, S10-OD018505), the American Cancer Society (125246-RSG-13-099-01-CCE), and the National Science Foundation of China (81401465, 51573096).

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Correspondence to Peng Huang or Weibo Cai.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Dawei Jiang, Hyung-Jun Im, and Haiyan Sun contributed equally to this work.

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Jiang, D., Im, HJ., Sun, H. et al. Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer. Eur J Nucl Med Mol Imaging 44, 1296–1305 (2017). https://doi.org/10.1007/s00259-017-3663-y

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  • DOI: https://doi.org/10.1007/s00259-017-3663-y

Keywords

  • Positron emission tomography (PET)
  • Human epidermal growth factor receptor 2 (HER2)
  • Pertuzumab
  • Ovarian cancer
  • Molecular imaging