Inhaled
hydrogen gas (H2) provides protection in rat models of human
acute lung injury (ALI). We previously reported that
biomarker imaging can detect oxidative stress and endothelial cell death in vivo in a rat model of ALI. Our objective was to evaluate the ability of Tc-hexamethylpropyleneamineoxime (HMPAO) and Tc-
duramycin to track the effectiveness of H2
therapy in vivo in the
hyperoxia rat model of ALI. Rats were exposed to room air (normoxia), 98% O2 + 2% N2 (
hyperoxia) or 98% O2 + 2% H2 (hyperoxia+H2) for up to 60 h. In vivo scintigraphy images were acquired following injection of Tc-HMPAO or Tc-
duramycin. For
hyperoxia rats, Tc-HMPAO and Tc-
duramycin lung uptake increased in a time-dependent manner, reaching a maximum increase of 270% and 150% at 60 h, respectively. These increases were reduced to 120% and 70%, respectively, in hyperoxia+H2 rats.
Hyperoxia exposure increased
glutathione content in lung homogenate (36%) more than hyperoxia+H2 (21%), consistent with increases measured in Tc-HMPAO lung uptake. In 60-h
hyperoxia rats,
pleural effusion, which was undetectable in normoxia rats, averaged 9.3 gram/rat, and lung tissue
3-nitrotyrosine expression increased by 790%. Increases were reduced by 69% and 59%, respectively, in 60-h hyperoxia+H2 rats. This study detects and tracks the
anti-oxidant and anti-apoptotic properties of H2
therapy in vivo after as early as 24 h of
hyperoxia exposure. The results suggest the potential utility of these SPECT
biomarkers for in vivo assessment of key cellular pathways in the pathogenesis of ALI and for monitoring responses to
therapies.