Minimally invasive detection of eosinophilic esophagitis-associated inflammation

Eosinophilic esophagitis (EoE) is an inflammatory disease characterized by infiltration of eosinophils into the esophageal wall. Current diagnosis requires analysis of small biopsy samples, leading to possible misdiagnosis if the tissue is sampled insufficiently. Here we develop a minimally invasive imaging method for the detection and mapping of eosinophil degranulation in EoE. The idea is to have patients swallow a radiolabeled contrast agent specific to eosinophil granule proteins and image the full length of the esophagus with single-photon emission computer tomography (SPECT/CT) imaging. First, we studied the patchiness of the disease by mapping an esophagectomy sample from a known EoE patient and found a significant variation in eosinophil distribution. Second, we determined and quantified eosinophil degranulation by electron microscopy from 9 randomly selected EoE patients and showed that the majority of eosinophils were associated with the release of intact granules into the epithelium. Third, we developed a radiolabeled contrast agent specific to eosinophil granule proteins. We synthesized Technetium-99m labeled heparin (99mTc-heparin) and studied the binding of the radiolabeled heparin to ex vivo biopsy tissues from patients. To evaluate the organ distribution, the dose assessment of orally administered 99mTcheparin was studied in healthy mice. These findings suggest that 99mTc-heparin can be used as a targeting agent to detect the eosinophils-associated inflammation.