Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 53, Issue 12, Pages 1984-1991Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.112.108498
Keywords
acute lung injury; apoptosis; oxidative stress
Funding
- NIH [UL1RR031973]
- NHLBI [24349]
- Department of Veterans Affairs
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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 Tc-99m-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue whereas Tc-99m-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 pre-exposed to either normoxia (21% O-2) or hyperoxia (85% O-2) for up to 21 d. For imaging, the rats were anesthetized and injected intravenously with either Tc-99m-HMPAO or Tc-99m-duramycin (both 37-74 MBq), and planar images were acquired using a high-sensitivity modular gamma-camera. Subsequently, Tc-99m-macroagreggated albumin (37 MBq, diameter 10-40 mu m) was injected intravenously, imaged, and used to define a lung region of interest. The lung-to-background ratio was used as a measure of lung uptake. Results: Hyperoxia exposure resulted in a 74% increase in Tc-99m-HMPAO lung uptake, which peaked at 7 d and persisted for the 21 d of exposure. Tc-99m-duramycin lung uptake was also maximal at 7 d of exposure but decreased to near control levels by 21 d. The sustained elevation of Tc-99m-HMPAO uptake suggests ongoing changes in lung redox status whereas cell death appears to have subsided by 21 d. Conclusion: These results suggest the potential use of Tc-99m-HMPAO and Tc-99m-duramycin as redox and cell-death imaging biomarkers, respectively, for the in vivo identification and assessment of different stages of lung injury.
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