Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY-025 Affibody PET/CT

Theranostics. 2016 Jan 1;6(2):262-71. doi: 10.7150/thno.13502. eCollection 2016.


Purpose: Positron Emission Tomography (PET) imaging of HER2 expression could potentially be used to select patients for HER2-targed therapy, predict response based on uptake and be used for monitoring. In this phase I/II study the HER2-binding Affibody molecule ABY-025 was labeled with (68)Ga-gallium ([(68)Ga]ABY-025) for PET to study effect of peptide mass, test-retest variability and correlation of quantified uptake in tumors to histopathology.

Experimental design: Sixteen women with known metastatic breast cancer and on-going treatment were included and underwent FDG PET/CT to identify viable metastases. After iv injection of 212±46 MBq [(68)Ga]ABY-025 whole-body PET was performed at 1, 2 and 4 h. In the first 10 patients (6 with HER2-positive and 4 with HER2-negative primary tumors), [(68)Ga]ABY-025 PET/CT with two different doses of injected peptide was performed one week apart. In the last six patients (5 HER2-positive and 1 HER2-negative primary tumors), repeated [(68)Ga]ABY-025 PET were performed one week apart as a test-retest of uptake in individual lesions. Biopsies from 16 metastases in 12 patients were collected for verification of HER2 expression by immunohistochemistry and in-situ hybridization.

Results: Imaging 4h after injection with high peptide content discriminated HER2-positive metastases best (p<0.01). PET SUV correlated with biopsy HER2-scores (r=0.91, p<0.001). Uptake was five times higher in HER2-positive than in HER2-negative lesions with no overlap (p=0.005). The test-retest intra-class correlation was r=0.996. [(68)Ga]ABY-025 PET correctly identified conversion and mixed expression of HER2 and targeted treatment was changed in 3 of the 16 patients.

Conclusion: [(68)Ga]ABY-025 PET accurately quantifies whole-body HER2-receptor status in metastatic breast cancer.

Keywords: 68Ga-gallium; Affibody; HER2-receptor; breast cancer metastases; clinical study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Female
  • Gallium Radioisotopes
  • Humans
  • Middle Aged
  • Multimodal Imaging
  • Neoplasm Metastasis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacokinetics*
  • Positron-Emission Tomography
  • Protein Binding
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Staphylococcal Protein A / chemistry
  • Tomography, X-Ray Computed


  • 68Ga-ABY-025
  • ABY-025
  • Gallium Radioisotopes
  • Peptide Fragments
  • Radiopharmaceuticals
  • Staphylococcal Protein A
  • ERBB2 protein, human
  • Receptor, ErbB-2