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Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY-025 Affibody PET/CT
Open accessAbstract
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.
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ImmunoPET: Concept, Design, and Applications
Wei, W., Rosenkrans, Z. T., Liu, J., Huang, G., Luo, Q.-Y., & Cai, W. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00738 · Cited by 484
Affibody Molecules in Biotechnological and Medical Applications
Ståhl, S., Gräslund, T., Eriksson Karlström, A., Frejd, F. Y., Nygren, P.-Å., & Löfblom, J. (2017) · Trends in Biotechnology · doi:10.1016/j.tibtech.2017.04.007 · Cited by 382
Affibody molecules as engineered protein drugs
Frejd, F. Y., & Kim, K.-T. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.35 · Cited by 225
Metadata
- Authors
- Sörensen, J., Velikyan, I., Sandberg, D., Wennborg, A., Feldwisch, J., Tolmachev, V., Orlova, A., Sandström, M., Lubberink, M., Olofsson, H., Carlsson, J., & Lindman, H.
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2016
- Volume
- 6
- Issue
- 2
- Pages
- 262-271
- ISSN
- 1838-7640 (ISSN-L)
- OpenAlex
- W2285875128
- Cited by
- 264
- References
- 27
- FWCI
- 13.30
- Type
- journal article
- Language
- en
- Open access
- gold
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- Sörensen, J., Velikyan, I., Sandberg, D., Wennborg, A., Feldwisch, J., Tolmachev, V., Orlova, A., Sandström, M., Lubberink, M., Olofsson, H., Carlsson, J., & Lindman, H. (2016). Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY-025 Affibody PET/CT. Theranostics. https://doi.org/10.7150/thno.13502
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