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First-in-Human Molecular Imaging of HER2 Expression in Breast Cancer Metastases Using the In-111-ABY-025 Affibody Molecule
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Medical Radiation Sciences.
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2014 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 55, no 5, 730-735 p.Article in journal (Refereed) Published
Abstract [en]

The expression status of human epidermal growth factor receptor type 2 (HER2) predicts the response of HER2-targeted therapy in breast cancer. ABY-025 is a small reengineered Affibody molecule targeting a unique epitope of the HER2 receptor, not occupied by current therapeutic agents. This study evaluated the distribution, safety, dosimetry, and efficacy of In-111-ABY-025 for determining the HER2 status in metastatic breast cancer. Methods: Seven patients with metastatic breast cancer and HER2-positive (n = 5) or - negative (n 5 2) primary tumors received an intravenous injection of approximately 100 mu g (similar to 140 MBq) of In-111-ABY-025. Planar gamma-camera imaging was performed after 30 min, followed by SPECT/CT after 4, 24, and 48 h. Blood levels of radioactivity, antibodies, shed serum HER2, and toxicity markers were evaluated. Lesional HER2 status was verified by biopsies. The metastases were located by F-18-FDG PET/CT 5 d before In-111-ABY-025 imaging. Results: Injection of In-111-ABY-025 yielded a mean effective dose of 0.15 mSv/MBq and was safe, well tolerated, and without drug-related adverse events. Fast blood clearance allowed high-contrast HER2 images within 4-24 h. No anti-ABY025 antibodies were observed. When metastatic uptake at 24 h was normalized to uptake at 4 h, the ratio increased in HER2-positive metastases and decreased in negative ones (P, < 0.05), with no overlap and confirmation by biopsies. In 1 patient, with HER2- positive primary tumor, In-111-ABY-025 imaging correctly suggested a HER2negative status of the metastases. The highest normal-tissue uptake was in the kidneys, followed by the liver and spleen. Conclusion: In-111-ABY- 025 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic breast cancer, regardless of ongoing HER2-targeted antibody treatment.

Place, publisher, year, edition, pages
2014. Vol. 55, no 5, 730-735 p.
Keyword [en]
Affibody, breast cancer metastases, clinical study, HER2 receptor, In-111 imaging
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-227273DOI: 10.2967/jnumed.113.131243ISI: 000335968000017OAI: oai:DiVA.org:uu-227273DiVA: diva2:731035
Funder
Swedish Cancer Society, 110565, 120415
Available from: 2014-06-30 Created: 2014-06-24 Last updated: 2017-12-05Bibliographically approved

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Sörensen, JensSandberg, DanSandström, MattiasFeldwisch, JoachimTolmachev, VladimirÅström, GunnarLubberink, MarkGarske-Roman, UlrikeCarlsson, JörgenLindman, Henrik
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