B7-H3-Targeted Contrast Agent for Ultrasonic Imaging of Breast Cancer

ABSTRACT Breast cancer is the second leading cause of cancer deaths in women in the United States and early detection can help improve survival While mammography is the current first line imaging technique for early breast cancer detection its diagnostic accuracy is limited in women with dense breast tissue Ultrasound is often performed as a second line test in women with dense breast tissue However due to its low specificity it results in many false positive findings with unnecessary biopsies with increased associated health care costs Dr Willmann and his group at Stanford have recently identified and validated B H as a novel highly specific neoangiogenesis marker in patients with breast cancer that allows differentiation of breast cancer from benign breast lesions with an AUC of up to In a preliminary study they tested an ultrasound contrast agent bearing antibodies to B H and showed in a transgenic mouse model that contrast enhanced ultrasound could detect small foci of breast cancer They have identified a peptide that binds to both murine and human B H Dr Unger and his group at NuvOx Pharma developed the world s selling microbubble MB ultrasound contrast agent and have industry leading expertise in targeting MB technologies The overall goal of this grant proposal is to develop a novel clinical grade B H targeted ultrasound contrast agent that allows detection and characterization of breast cancer with both high sensitivity and specificity In this collaborative effort we will create bioconjugates of the already identified peptide to B H incorporate them into newly designed clinical grade ultrasound contrast microbubbles MB confirm their binding to B H in vitro under flow shear stress conditions and then confirm efficacy in a transgenic mouse model of breast cancer development We will label the molecularly targeted MB with a fluorescent dye to allow in situ confirmation of in vivo B H target binding using microscopy Successful completion of the Aims of this project may subsequently support formal development of B H targeted MB as a new drug candidate in Phase II Project Narrative Current approaches for the diagnosis of early breast cancer in particular in women with dense breast tissue have major limitations leading to delayed or missed diagnoses as well as false positive results This research will develop a new clinical grade ultrasound contrast agent to enable rapid and effective detection and characterization of breast cancer at an early still curable stage