title: Breast Cancer Detection by B7-H3-Targeted Ultrasound Molecular Imaging.
abstract: Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T-cell coregulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor, and malignant breast pathologies for diagnostic purposes. Through an IHC analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients.
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
authors.forename: Sunitha V
authors.initials: SV
authors.lastname: Bachawal
authors.affiliation: Department of Pathology, Stanford University, Stanford, California. Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Jensen
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
authors.forename: Katheryne E
authors.initials: KE
authors.lastname: Wilson
authors.affiliation: Department of Health, Research and Policy, Stanford University, Stanford, California.
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
authors.forename: Amelie M
authors.initials: AM
authors.lastname: Lutz
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California. willmann@stanford.edu.
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Willmann
mesh_terms: D000818:Animals; D060887:B7 Antigens / Q000032:analysis* / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000000981:diagnostic imaging; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods*; D014463:Ultrasonography / Q000379:methods
chemical_list: D060887:B7 Antigens; D014408:Biomarkers, Tumor; C423237:CD276 protein, human; C486038:Cd276 protein, mouse