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

• Published in: Clinical cancer research Vol. 26; no. 9; pp. 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: Journal Article
• Language: English
• Published: United States 01-05-2020
• 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
• DOI: 10.1158/1078-0432.CCR-19-1655
• EISSN: 1557-3265
• ISSN: 1078-0432

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.