Abstract 1727: Ultrasound Detection of Molecular Epitopes Critical For Thrombosis and Restenosis With Tissue Factor-Targeted Perfluorocarbon Nanoparticles
Introduction: Targeted liquid perfluorocarbon nanoparticles (PFC-NP) were the first described contrast agents for ultrasound molecular imaging of epitopes such as fibrin in thrombi, alpha-v-beta3-integrin angiogenic markers in tumor neovasculature, and tissue factor (TF) in thrombosis. This study sought to quantify the relationship between augmented reflectivity induced by targeting PFC-NP to cell surface TF and the measured density of bound PFC-NP.
Methods: In one preparation, avidin-coated agar disks were exposed to biotinylated PFC-NP to create a single thin layer of targeted NP on the surface. In a second preparation, multiple layers of PFC-NP were bound to the surface of cultured smooth muscle cells (constitutively expressing TF) via complexation with an anti-TF monoclonal Ab using biotin-avidin intermediaries. Also, non-echogenic oil-based NP were competed against PFC-NP to define the PFC concentration dependence of contrast enhancement. Ultrasonic backscatter was compared with the amount of bound PFC determined by gas chromatography.
Results: Significant enhancement was observed for samples exposed to PFC-NP relative to samples left untreated or targeted only with oil-based NP (>7.5 dB, p<0.0001). Reflectivity increased with increasing levels of bound PFC-NP and exhibited an apparent asymptote at the maximum PFC-NP concentrations. This behavior accords with predictions of reflectivity using a “transmission-line” model.
Conclusions: Targeted PFC-NP for acoustic molecular imaging are capable of registering sparse concentrations of pathological molecules such cellular tissue factor, which are predictable from simple mathematical models.