LAUSR

With regard to biomarker expression, tumors are heterogeneous media displaying intra- and interpatient variability. Ultrasound molecular imaging (USMI) is a newly developed tool that can characterize heterogeneous tumors. Here, we focus on Netrin-1-overexpressing breast cancer. A newly developed targeted therapy interfering with Netrin-1 requires patient stratification. We developed Netrin-1-targeted microbubbles (MBs) and assessed USMI for identification of Netrin-1-positive breast cancer. In vitro flow chamber assays showed specific binding of anti-Netrin-1-MBs to human and murine breast cancer cell lines overexpressing Netrin-1. In vivo, in Netrin-1-positive transgenic or implanted mouse breast cancer models, USMI showed significantly increased signals with Netrin-1-targeted MBs, compared with isotype control MBs and targeted MBs after blocking of Netrin-1:—44.8%, 32.0%, 33.7% intensity for MBsNetrin-1, MBsIsotype, or after blocking, resp., in MMTV tumors;—28.2%, 13.7%, 13.4%, resp., in SKBR7 tumors;—6...