2. Academic Validation
  3. Imaging and monitoring HER2 expression in breast cancer during trastuzumab therapy with a peptide probe 99mTc-HYNIC-H10F

Imaging and monitoring HER2 expression in breast cancer during trastuzumab therapy with a peptide probe 99mTc-HYNIC-H10F

  • Eur J Nucl Med Mol Imaging. 2020 Oct;47(11):2613-2623. doi: 10.1007/s00259-020-04754-6.
Yue Wu # 1,  Liqiang Li # 1,  Zihua Wang 2,  Jiyun Shi 3,  Zhiyuan Hu 2,  Shi Gao 4,  Weibing Miao 5,  Qingjie Ma 4,  Chengyan Dong 6 7,  Fan Wang 8 9
Affiliations

Affiliations

  • 1 Medical Isotopes Research Center and Department of Radiation Medicine, State Key Laboratory of Natural and Biomimetic Drugs, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
  • 2 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology of China, Beijing, 100190, China.
  • 3 Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100010, China.
  • 4 Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Jilin, 130033, China.
  • 5 Department of Nuclear Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
  • 6 Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100010, China. chengyan.dong@ge.com.
  • 7 GE Healthcare, Beijing, 100126, China. chengyan.dong@ge.com.
  • 8 Medical Isotopes Research Center and Department of Radiation Medicine, State Key Laboratory of Natural and Biomimetic Drugs, School of Basic Medical Sciences, Peking University, Beijing, 100191, China. wangfan@bjmu.edu.cn.
  • 9 Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100010, China. wangfan@bjmu.edu.cn.
  • # Contributed equally.
PMID: 32170344 DOI: 10.1007/s00259-020-04754-6
Abstract

Purpose: The novel molecular imaging probe 99mTc-HYNIC-H10F was developed for patient screening and efficacy monitoring of trastuzumab therapy by SPECT imaging of HER2 expression in breast Cancer.

Methods: 99mTc-HYNIC-H10F was developed by labeling H10F peptide with 99mTc following an optimized protocol. Biodistribution and SPECT/CT were performed in mouse models bearing HER2-positive SK-BR3 and HER2-negative MDA-MB-231 human breast Cancer xenografts, respectively. The treatment response to trastuzumab was monitored and quantified by SPECT/CT in two HER2-positive breast Cancer models (SK-BR3 and MDA-MB-361). The preliminary clinical study was performed in two patients with breast Cancer.

Results: SPECT/CT with 99mTc-HYNIC-H10F showed that the SK-BR3 tumors were clearly visualized, while the signals from MDA-MB-231 tumors were much lower. The tumor uptake of 99mTc-HYNIC-H10F could be blocked by excess unlabeled H10F peptide but not by excess trastuzumab. The growth of two HER2-positive tumors was prominently suppressed at day 11 post-treatment. However, SPECT/CT reflected much earlier therapy response at day 4 post-treatment. The HER2 expression in tumors of breast Cancer patients could be detected by 99mTc-HYNIC-H10F SPECT/CT imaging.

Conclusions: 99mTc-HYNIC-H10F specifically accumulates in HER2-positive tumors. Compared with trastuzumab, 99mTc-HYNIC-H10F binds to a different domain of HER2 antigen, providing new opportunities to monitor HER2 expression levels before/during/after trastuzumab treatment for more effective personalized treatment.

Keywords

Breast cancer; HER2; SPECT/CT; Therapy monitoring; Trastuzumab.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P11761
    H10F与HYNIC偶联物
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