Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging

Our goal is to develop minimally invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently, there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in radiologic terrorism. Our previous studies have shown that a single dose of 15 Gy of x-rays to the thorax causes severe pneumonitis in rats by 68 wk. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 wk after radiation. Methods: We used 2 functional SPECT probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of Tc-99m-macroaggregated albumin. Perfused volume was determined by comparing the volume of distribution of Tc-99m-macroaggregated albumin to the anatomic lung volume obtained by small-animal CT. A second probe, Tc-99m-labeled Duramycin, which binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. Results: The perfused volume of lung was decreased by about 25% at 1, 2, and 3 wk after receipt of 15 Gy, and Tc-99m-Duramycin uptake was more than doubled at 2 and 3 wk. There was no change in body weight, breathing rate, or lung histology between irradiated and nonirradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 wk after 15 Gy of irradiation. Conclusion: Our results suggest that SPECT biomarkers have the potential to predict radiation injury to the lungs before substantial functional or histologic damage is observed. Early prediction of radiation pneumonitis in time to initiate mitigation will benefit those exposed to radiation in the context of therapy, accidents, or terrorism.