Non-invasive ultrasound to identify eosinophil granule proteins in eosinophilic esophagitis

Although traditional microbubble contrast agents are bright, the high contrast of gas bubbles and air-water interfaces in the upper gastrointestinal tract renders these agents less useful for diagnosing diseases such as eosinophilic esophagitis, a disease characterized by patchy infiltration of eosinophils into the esophagus. Here we report a first-in-class ultrasound contrast enhancement agent composed of echogenic insulin particles, which are labeled with molecular recognition elements to diagnose eosinophil-associated diseases. We prepared solid echogenic insulin particles, tethered antibodies to eosinophil granule major basic protein 1 (MBP-1) to their surfaces and experimentally evaluated binding of these agents to MBP-1 on ex vivo non-human primate esophagi. We found that insulin particles can be readily observed by ultrasound and bind to MBP-1-coated esophagi within minutes. Our results suggest the potential of this new class of solid contrast agents to image, diagnose and improve management of eosinophilic esophagitis.