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13. Reply

Author

Saffari, Hedieh, primary, Baer, Krista, additional, Boynton, Kathleen K., additional, Gleich, Gerald J., additional, and Peterson, Kathryn A., additional

Published
2017
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15. Minimally invasive detection of eosinophilic esophagitis-associated inflammation

Author

Saffari, Hedieh

Subjects
Inflammation, Eosinophilic esophagitis, Heparin, Technetium-99m, Eosinophils granule protein, Radioimaging
Abstract

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.

Published
2014
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25. Oral Administration of 99m Technetium-Labeled Heparin in Eosinophilic Esophagitis.

Author

Saffari H, Peterson KA, Leiferman KM, Stabin MG, Krstyen JJ, Clayton FC, Pease LF 3rd, Yap JT, Hoffman JM, and Gleich GJ

Subjects
Administration, Oral, Adult, Esophagoscopy, Humans, Male, Middle Aged, Tissue Distribution, Whole Body Imaging, Eosinophilic Esophagitis diagnostic imaging, Heparin administration & dosage, Organotechnetium Compounds administration & dosage, Radiopharmaceuticals administration & dosage, Tomography, Emission-Computed, Single-Photon
Abstract

Objective: To determine if heparin labeled with 99m Technetium ( 99m Tc) could be an imaging probe to detect eosinophil-related inflammation in eosinophilic esophagitis and to determine the biodistribution and radiation dosimetry of 99m Tc-heparin oral administration using image-based dosimetry models with esophageal modeling., Methods: Freshly prepared 99m Tc-heparin was administered orally to 5 research subjects. Radioactivity was measured by whole-body scintigraphy and single-photon emission computed tomography during the 24 hours postadministration. Following imaging, endoscopic examination was performed. The biodistribution of esophageal radioactivity was compared with endoscopic findings, eosinophil counts in biopsy tissues, and immunostaining for eosinophil granule major basic protein-1 (eMBP1). These studies were conducted from July 1, 2013, until April 22, 2017., Results: Oral administration of 99m Tc-heparin was well tolerated in all 5 subjects. The entire esophagus could be visualized dynamically during oral administration. Bound esophageal radioactivity marked areas of inflammation as judged by endoscopy scores, by eosinophils per high power field and by localization of eMBP1 using immunostaining. Ninety percent of the radioactivity did not bind to the esophagus and passed through the gastrointestinal tract., Conclusion: The biodistribution of ingested 99m Tc-heparin is almost exclusively localized to the gastrointestinal tract. Radiation exposure was highest in the lower gastrointestinal tract and was comparable with other orally administered diagnostic radiopharmaceuticals. The use of swallowed 99m Tc-heparin may aid in assessing eosinophil-related inflammation in the esophagus., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Published
2020
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26. ⁹⁹mTechnetium-labeled heparin: a new approach to detection of eosinophilic esophagitis-associated inflammation.

Author

Saffari H, Krstyen JJ, Gonzalez C, Clayton FC, Leiferman KM, Gleich GJ, Peterson KA, and Pease LF 3rd

Subjects
Cell Degranulation, Eosinophil Cationic Protein analysis, Eosinophil Cationic Protein metabolism, Esophagus pathology, Humans, Protein Binding, Radioligand Assay, Tomography, Emission-Computed, Single-Photon, Eosinophilic Esophagitis diagnostic imaging, Eosinophils immunology, Esophagus diagnostic imaging, Heparin, Organotechnetium Compounds, Technetium
Published
2013
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