Engineering Commons^™

The Feasibility Of Imaging Myocardial Ischemic/Reperfusion Injury Using 99mTc-Labeled Duramycin In A Porcine Model, Lei Wang, Feng Wang, Wei Fang, Steven E. Johnson, Said H. Audi, Michael Zimmer, Thomas A. Holly, Daniel C. Lee, Bao Zhu, Haibo Zhu, Ming Zhao

Biomedical Engineering Faculty Research and Publications

When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. ^99mTc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of ^99mTc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia–reperfusion injury.

Methods

The clearance and distribution of intravenously injected ^99mTc-duramycin were characterized in sham-operated animals (n = 5). In a closed chest model of myocardial ischemia, coronary occlusion was induced …

In Vivo Detection Of Hyperoxia-Induced Pulmonary Endothelial Cell Death Using 99mTc-Duramycin, Said H. Audi, Elizabeth R. Jacobs, Ming Zhao, David L. Roerig, Steven T. Haworth, Anne V. Clough

Biomedical Engineering Faculty Research and Publications

Introduction

^99mTc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury.

Methods

Rats were exposed to room air (normoxic) or > 98% O₂ for 48 or 60 hours. DU was injected i.v. in anesthetized rats, scintigraphy images were acquired at steady-state, and lung DU uptake was quantified from the images. Post-mortem, the lungs were removed for histological studies. Sequential lung sections were immunostained …

Differential Lung Uptake Of 99mtc-Hexamethylpropyleneamine Oxime And 99mtc-Duramycin In The Chronic Hyperoxia Rat Model, Anne V. Clough, Said H. Audi, Steven Thomas Haworth, David L. Roerig

Biomedical Engineering Faculty Research and Publications

Noninvasive radionuclide imaging has the potential to identify and assess mechanisms involved in particular stages of lung injury that occur with acute respiratory distress syndrome, for example. Lung uptake of ^99mTc-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue whereas ^99mTc-duramycin, a new marker of cell injury, senses cell death via apoptosis or necrosis. Thus, we investigated changes in lung uptake of these agents in rats exposed to hyperoxia for prolonged periods, a common model of acute lung injury. Methods: Male Sprague–Dawley rats were preexposed to either normoxia (21% O …

99mTc-Labeled C2a Domain Of Synaptotagmin I As A Target-Specific Molecular Probe For Noninvasive Imaging Of Acute Myocardial Infarction, Ming Zhao, Xiaoguang Zhu, Shundong Ji, Jundong Zhou, Kutlan S. Ozker, Wei Fang, Robert C. Molthen, Robert S. Hellman

Biomedical Engineering Faculty Research and Publications

Abstract: The exposure of phosphatidylserine (PtdS) is a common molecular marker for both apoptosis and necrosis and enables the simultaneous detection of these distinct modes of cell death. Our aim was to develop a radiotracer based on the PtdS-binding activity of the C2A domain of synaptotagmin I and assess ^99mTc-C2A-GST (GST is glutathione S-transferase) using a reperfused acute myocardial infarction (AMI) rat model. Methods: The binding of C2A-GST toward apoptosis and necrosis was validated in vitro. After labeling with ^99mTc via 2-iminothiolane thiolation, radiochemical purity and radiostability were tested. Pharmacokinetics and biodistribution were studied in healthy rats. …