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

被引：34

作者：

Bam, Rakesh ^{[1
]}

Lown, Patrick S. ^{[2
]}

Stern, Lawrence A. ^{[2
]}

Sharma, Karina ^{[1
]}

Wilson, Katheryne E. ^{[1
]}

Bean, Gregory R. ^{[3
]}

Lutz, Amelie M. ^{[1
]}

Paulmurugan, Ramasamy ^{[1
]}

Hackel, Benjamin J. ^{[2
]}

Dahl, Jeremy ^{[1
]}

Abou-Elkacem, Lotfi ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA

[2] Univ Minnesota, Chem Engn & Mat Sci, Minneapolis, MN USA

[3] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

来源：

CLINICAL CANCER RESEARCH | 2020年 / 26卷 / 09期

关键词：

CONTRAST-ENHANCED ULTRASOUND; TUMOR ANGIOGENESIS; DENSE BREASTS; MICROBUBBLES; US; WOMEN; STABILIZATION; THERAPY; AGENTS; MOUSE;

D O I：

10.1158/1078-0432.CCR-19-1655

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: 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. Experimental Design: Binding of ABY(B7-H3) was confirmed with soluble and cell-surface B7-H3 by flow cytometry. MB were functionalized with ABY(B7-H3) or anti-B7-H3-antibody (Ab(B7-H3)). Control and targeted MB were tested for binding to hB7-H3-expressing cells (MS1h(B7-H3)) under shear stress conditions. US imaging was performed with MBABY-B7-H3 in an orthotopic mouse model of human MDA-MB-231 coimplanted with MS1(hB7-H3) or control MS1WT cells and a transgenic mouse model of breast cancer development. Results: ABYB7- H3 specifically binds to MS1(hB7-H3) and murine-B7-H3-expressing monocytes. MBABY-B7-H3 (8.5 +/- 1.4 MB/cell) and MBAb-B7-H3 (9.8 +/- 1.3 MB/cell) showed significantly higher ( P < 0.0001) binding to the MS1(hB7-H3) cells compared with control MBNon-targeted (0.5 +/- 0.1 MB/cell) under shear stress conditions. In vivo, MBABY-B7-H3 produced significantly higher ( P < 0.04) imaging signal in orthotopic tumors coengrafted with MS1(hB7-H3) (8.4 +/- 3.3 a. u.) compared with tumors with MS1(WT) cells (1.4 +/- 1.0 a.u.). In the transgenic mouse tumors, MBABY-B7-H3 (9.6 +/- 2.0 a.u.) produced higher (P < 0.0002) imaging signal compared with MBNon- targeted (1.3 +/- 0.3 a.u.), whereas MBABY-B7-H3 signal in normal mammary glands and tumors with B7-H3 blocking significantly reduced (P < 0.02) imaging signal. Conclusions: MBABY-B7-H3 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.

引用

页码：2140 / 2150

页数：11

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