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

^99mTc-hexamethylpropyleneamine oxime (HMPAO) and ^99mTc-duramycin in vivo imaging detects pulmonary oxidative stress and cell death, respectively, in rats exposed to &gt;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 (<i>P</i> &lt; 0.01) in hyperoxia compared with normoxia rats, respectively. On the other hand, uptake of ^99mTc-HMPAO in H-T + 60 was 24% greater (<i>P</i> &lt; 0.01) than in H-T rats, but ^99mTc-duramycin uptake was not significantly different (<i>P</i> = 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 <i>complex IV</i> 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.