In vivo molecular imaging stratifies rats with different susceptibilities to hyperoxic acute lung injury

Said H. Audi*, Pardis Taheri, Ming Zhao, Kurt Hu, Elizabeth R. Jacobs, Anne V. Clough

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


99mTc-hexamethylpropyleneamine oxime (HMPAO) and 99mTc-duramycin in vivo imaging detects pulmonary oxidative stress and cell death, respectively, in rats exposed to >95% O2 (hyperoxia) as a model of acute respiratory distress syndrome (ARDS). Preexposure to hyperoxia for 48 h followed by 24 h in room air (H-T) is protective against hyperoxia-induced lung injury. This study’s objective was to determine the ability of 99mTc-HMPAO and 99mTc-duramycin to track this protection and to elucidate underlying mechanisms. Rats were exposed to normoxia, hyperoxia for 60 h, H-T, or H-T followed by 60 h of hyperoxia (H-T + 60). Imaging was performed 20 min after intravenous injection of either 99mTc-HMPAO or 99mTc-duramycin. 99mTc-HMPAO and 99mTc-duramycin lung uptake was 200% and 167% greater (P < 0.01) in hyperoxia compared with normoxia rats, respectively. On the other hand, uptake of 99mTc-HMPAO in H-T + 60 was 24% greater (P < 0.01) than in H-T rats, but 99mTc-duramycin uptake was not significantly different (P = 0.09). Lung wet-to-dry weight ratio, pleural effusion, endothelial filtration coefficient, and histological indices all showed evidence of protection and paralleled imaging results. Additional results indicate higher mitochondrial complex IV activity in H-T versus normoxia rats, suggesting that mitochondria of H-T lungs may be more tolerant of oxidative stress. A pattern of increasing lung uptake of 99mTc-HMPAO and 99mTc-duramycin correlates with advancing oxidative stress and cell death and worsening injury, whereas stable or decreasing 99mTc-HMPAO and stable 99mTc-duramycin reflects hyperoxia tolerance, suggesting the potential utility of molecular imaging for identifying at-risk hosts that are more or less susceptible to progressing to ARDS.

Original languageEnglish (US)
Pages (from-to)L410-L422
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number4
StatePublished - Oct 2022


  • acute respiratory distress syndrome (ARDS)
  • duramycin
  • glutathione
  • hexamethylpropyleneamine oxime (HMPAO)
  • single photon emission computed tomography (SPECT)

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology
  • Pulmonary and Respiratory Medicine
  • Cell Biology


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