Biodistribution of orally administered 99mTc-heparin to assess eosinophilic esophagitis associated inflammation

Abstract

Here we explore the biodistribution of ^99mTc-heparin, an orally administered radiopharmaceutical candidate expected to identify localized inflammation in eosinophilic esophagitis (EoE). Heparin binds to eosinophil granule proteins in inflamed regions of gastrointestinal (GI) organs, and ^99mTc signals their location. This article evaluates the biodistribution of this conjugate first within the esophagus by modeling the reactive transport of ^99mTc-heparin based on the kinetics of ^99mTc-heparin binding to non-human primate esophagi and second in the remainder of the body by measuring organ specific uptake using single-photon emission computed tomography/computed tomography imaging. Results show that binding and dissociation rate constants remain similar, and that optimal imaging occurs after drinking of the agent is complete. We also find that ^99mTc-heparin remains within the GI tract simply transporting through the gut and out. These findings provide a new avenue to clinically explore the utility of ^99mTc-heparin to detect eosinophil associated inflammation in the GI tract.