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*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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 60hours. 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 for caspase activation and endothelial and epithelial cells. Results: Lung DU uptake increased significantly (p<0.001) by 39% and 146% in 48-hr and 60-hr exposed rats, respectively, compared to normoxic rats. There was strong correlation (r2=0.82, p=0.005) between lung DU uptake and the number of cleaved caspase 3 (CC3) positive cells, and endothelial cells accounted for more than 50% of CC3 positive cells in the hyperoxic lungs. Histology revealed preserved lung morphology through 48hours. By 60hours there was evidence of edema, and modest neutrophilic infiltrate. Conclusions: Rat lung DU uptake in vivo increased after just 48hours of >98% O2 exposure, prior to the onset of any substantial evidence of lung injury. These results suggest that apoptotic endothelial cells are the primary contributors to the enhanced DU lung uptake, and support the utility of DU imaging for detecting early endothelial cell death in vivo.

Original languageEnglish (US)
Pages (from-to)46-52
Number of pages7
JournalNuclear Medicine and Biology
Volume42
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Acute lung injury
  • Apoptosis
  • Lung imaging

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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