Figure 3. PBCA-based polymeric MB for molecular imaging.
A: Schematic depiction of the retention of ligand-targeted MB for contrast-enhanced US imaging of endothelial biomarkers in atherosclerosis. B: Ex vivo binding of rhodamine-labeled VCAM-1-targeted MB to an explanted murine carotid artery after TNF-α stimulation, as assessed by 3D two-photon laser scanning microscopy (3D-2PM). VCAM-1-targeted MB bind to activated endothelial cells and show retention under physiological shear stress (upper panel), whereas untargeted MB hardly associate with inflamed blood vessels (lower panel). Rhodamine-labeled MB are shown in red, elastin autofluorescence in green, and second harmonic generation imaging of collagen is depicted in blue. C: Illustration of the binding of targeted MB for contrast-enhanced US of angiogenesis biomarkers during tumor progression. D: Non-linear molecular US imaging of peptide-modified MB recognizing E-selectin on tumor blood vessels in subcutaneous A431 xenograft tumors. Signal enhancement (in blue) as a difference of contrast intensity before (upper panel) and after (lower panel) MB destruction by destructive US pulses allows for the assessment of E-selectin expression, and analysis of tumor vascularization and angiogenesis.