Efficacy of Affibody-Based Ultrasound Molecular Imaging of Vascular B7-H3 for Breast Cancer Detection

Human B7-H3 (hB7-H3) is a promising molecular imaging target differentially expressed on the neovasculature of breast cancer and has been validated for preclinical ultrasound (US) imaging with anti-B7-H3-antibody-functionalized microbubbles (MB). However, smaller ligands such as affibodies (ABY) are...

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Published in:Clinical cancer research 2020-05, Vol.26 (9), p.2140-2150
Main Authors: Bam, Rakesh, Lown, Patrick S, Stern, Lawrence A, Sharma, Karina, Wilson, Katheryne E, Bean, Gregory R, Lutz, Amelie M, Paulmurugan, Ramasamy, Hackel, Benjamin J, Dahl, Jeremy, Abou-Elkacem, Lotfi
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - chemistry
Antibodies, Monoclonal - immunology
B7 Antigens - immunology
B7 Antigens - metabolism
Breast Neoplasms - blood supply
Breast Neoplasms - diagnostic imaging
Breast Neoplasms - immunology
Breast Neoplasms - metabolism
Contrast Media - chemistry
Disease Models, Animal
Female
Mice
Mice, Nude
Mice, Transgenic
Microbubbles
Molecular Imaging - methods
Neovascularization, Pathologic - immunology
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - pathology
Ultrasonography - methods
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Summary:Human B7-H3 (hB7-H3) is a promising molecular imaging target differentially expressed on the neovasculature of breast cancer and has been validated for preclinical ultrasound (US) imaging with anti-B7-H3-antibody-functionalized microbubbles (MB). However, smaller ligands such as affibodies (ABY) are more suitable for the design of clinical-grade targeted MB. Binding of ABY was confirmed with soluble and cell-surface B7-H3 by flow cytometry. MB were functionalized with ABY or anti-B7-H3-antibody (Ab ). Control and targeted MB were tested for binding to hB7-H3-expressing cells (MS1 ) under shear stress conditions. US imaging was performed with MB in an orthotopic mouse model of human MDA-MB-231 coimplanted with MS1 or control MS1 cells and a transgenic mouse model of breast cancer development. ABY specifically binds to MS1 and murine-B7-H3-expressing monocytes. MB (8.5 ± 1.4 MB/cell) and MB (9.8 ± 1.3 MB/cell) showed significantly higher ( < 0.0001) binding to the MS1 cells compared with control MB (0.5 ± 0.1 MB/cell) under shear stress conditions. , MB produced significantly higher ( < 0.04) imaging signal in orthotopic tumors coengrafted with MS1 (8.4 ± 3.3 a.u.) compared with tumors with MS1 cells (1.4 ± 1.0 a.u.). In the transgenic mouse tumors, MB (9.6 ± 2.0 a.u.) produced higher ( < 0.0002) imaging signal compared with MB (1.3 ± 0.3 a.u.), whereas MB signal in normal mammary glands and tumors with B7-H3 blocking significantly reduced ( < 0.02) imaging signal. MB enhances B7-H3 molecular signal in breast tumors, improving cancer detection, while offering the advantages of a small size ligand and easier production for clinical imaging.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-19-1655