(678h) Synthesis and Characterization of Biomimetic Echogenic Microparticles for Use As Ultrasound Contrast Agents

Esophageal diseases can be difficult to accurately diagnose due to heterogeneity in the distribution of diseased tissues. For example, eosinophilic esophagitis (EoE) is characterized by patchy invasion of eosinophils, a type of white blood cell. Currently, 5-8 biopsies are recommended for EoE diagnosis, and if even one is found to have accumulations of eosinophils, the patient is said to have EoE. However, this procedure is invasive and up to 20% of patients may be misdiagnosed due to the patchiness of eosinophil invasion. New diagnostic measures utilizing biomimetic ultrasound contrast enhancement agents may provide a more effective, patient friendly, and efficient way to diagnose EoE by signally eosinophil concentrations throughout the esophagus.

Here we report our efforts to evaluate structure-function relationships for new biomimetic particles that mimic naturally echogenic but toxic amyloids fibrils found in cardiac tissue. These particles comprise insulin approximately 0.1-3.0 mm in diameter that provides an ecogenic signal labeled with eosinophil specific antibodies to facilitate the diagnosis of EoE. These agents were synthesized under varying conditions to evaluate the parameters that may affect microparticle structure. Our study focuses on the effect of temperature, concentration, incubation time, pH, and mixing on echogenicity. Our results show that insulin particles provide strong ultrasound contrast and bind to the granule proteins even at air-water interfaces—a challenging environment for other ultrasound contrast agents. These results indicate the potential of this new class of contrast agents to diagnose a broad range of lung and gastrointestinal diseases.