8B-1 Polymer Contrast Particles For Cellular Imaging With Ultrasound and MRI

This study describes the fabrication and characterization of a targeted polymer-based contrast agent for multi-modal ultrasound and magnetic resonance imaging, providing the potential for cell labeling and tracking in vivo. Ultrasound and MRI contrast enhancing particles (UMCEP) were fabricated using a biodegradable polymer, poly(lactic-co-glycolic) acid (PLGA) particles encapsulating octafluoropropane and monocrystalline iron-oxide nanoparticles (MION). Targeting was achieved using an avidin-palmitate stabilizer which provided a high density of sites for conjugation of biotinylated ligands. Particle size analysis of the UMCEPs revealed a heterogeneous distribution of particles sizes with a mean diameter close to 1 mum (0.88 mumplusmn0.03, s.e.m) and scanning electron micrographs (SEM) showed a pronounced increase in surface roughness of avidin-coated UMCEPs compared to plain UMCEPs. UMCEPs caused a nine-fold increase in signal intensity compared to background at 40 MHz and higher harmonics (80 MHz and 120 MHZ peaks) were observed in the frequency spectra at multi-cycle, medium pressure excitation regimens. MRI phantom studies with UMCEPs showed T2-weighted signal darkening, with a measured relaxivity of 7.4 s^-1 at a concentration of 4 mg/ml of particles. Cell culture experiments with UMCEPs conjugated to human transferrin showed a two-fold increase in uptake of targeted UMCEPs by TfR expressing (TfR+) cells (3.46plusmn1.21 s.e.m particles/cell) compared to TfR negative (TfR-, control) (1.66plusmn0.32 s.e.m particles/cell).