In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles

摘要: Nucleolin (NCL) plays an important role in tumor vascular development. An increased endothelial expression level of NCL has been related to cancer aggressiveness and prognosis detected clinically advanced tumors. Here, with a peptide targeted (F3 peptide), we created NCL-targeted microbubble (MB) compared the performance F3-conjugated MBs non-targeted (NT) both in vitro in vivo. In study, bound 433 times more than NT NCL-expressing cell line, while pretreating cells 0.5 mM free F3 reduced binding by 84%, n = 4, p < 0.001. We then set out create method extract wash-in wash-out kinetics accumulation following single injection MBs. order accomplish this, series ultrasound frames (a clip) was recorded at time subsequent points. Each pixel within this clip analyzed for minimum intensity projection (MinIP) average (AvgIP). found that MinIP robustly demonstrates enhanced over range diameters evaluated here (2–8 mm), difference between AvgIP quantifies inflow kinetics. The clearance were similar unbound MBs, control (non-targeted) scrambled agents. Targeted agent confirmed high amplitude pulse two-dimensional Fourier Transform technique. summary, provide new imaging molecular vasculature, have validated metrics assess using low mechanical index strategies potential use human studies.