Measuring HER2-receptor expression in metastatic breast cancer using [68Ga]ABY-025 Affibody PET/CT

Jens Sörensen, Irina Velikyan, Dan Sandberg, Anders Wennborg, Joachim Feldwisch, Vladimir Tolmachev, Anna Orlova, Mattias Sandström, Mark Lubberink, Helena Olofsson, Jörgen Carlsson, Henrik Lindman

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)

Abstract

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 68Ga-gallium ([68Ga]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 [68Ga]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), [68Ga]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 [68Ga]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. [68Ga]ABY-025 PET correctly identified conversion and mixed expression of HER2 and targeted treatment was changed in 3 of the 16 patients. Conclusion: [68Ga]ABY-025 PET accurately quantifies whole-body HER2-receptor status in metastatic breast cancer.

Original languageEnglish
Pages (from-to)262-271
Number of pages10
JournalTheranostics
Volume6
Issue number2
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • Ga-gallium
  • Affibody
  • Breast cancer metastases
  • Clinical study
  • HER2-receptor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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