Pet imaging for evaluation of inflammatory response in a murine model of acute respiratory failure

Background: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening form of acute respiratory failure, with a still high mortality. Aspiration pneumonitis is a clinical disorder that, entailing a direct lung injury, is associated to ARDS. It is characterized by an acute inflammatory response with neutrophilic recruitment into the lung and a late fibrotic evolution of injury. This study investigates whether the use of PET could allow to monitor this inflammatory response and its correlation with the later fibroproliferative phase in an experimental model of acute respiratory failure. Since to date no specific therapeutic strategies are available for ARDS patients, we tested the effects of exogenous surfactant treatment on lung injury evolution, by monitoring it with CT-PET imaging. Methods: Hydrochloric acid (0,1M) was instilled (1,5 ml/kg) into the right bronchus of mice. The study was divided into three parts. Time-course experiment: four groups of mice underwent micro-CT and micro-PET scans and sacrificed at different time point (6hrs, 24 hrs, 48 hrs and 7 days after surgery) to assess arterial blood gases, histology and bronchoalveolar lavage (BAL). Long-term experiment: one group of mice underwent a micro-CT scan 1 hour after lung injury and a series of [18F]FDG-PET at the same time points. 21 days after respiratory static compliance was measured and lung tissue was collected in order to measure the OH-proline content. Treatment experiment: two groups of mice were treated with exogenous surfactant (Curosurf ®) or vehicle (sterile saline 0.9 %) three hours after HCl instillation. Animals underwent micro-CT and a series of micro-PET scans. 21 days after they were sacrificed to measure lung mechanics and collagen deposition. Results: Histological analysis showed a rapid recruitment of neutrophils into the damaged lung 6 hours after injury, with a peak after 24 hours. Macrophages, as expected, reached the peak after 48 hours. [18F]FDG signal, as inflammation marker, showed similar time course to that of recruited inflammatory cells (sum of two cell types). Mice that were sacrificed 21 days after the surgery were characterized by a correlation between a reduced respiratory static compliance and a high PET signal 7 days after lung injury. PET signal correlated also with collagen content. This correlation was confirmed in treatment experiment, in which we found that exogenous surfactant administration improved lung fibrotic evolution, by reducing collagen deposition. Conclusions: This study demonstrated the possibility to use PET imaging to follow the inflammatory response also in longitudinal studies. Moreover a correlation between a persistence of inflammatory process and fibrotic evolution was showed. We speculate that it is possible that acute treatments of the inflammation capable of reducing the fibroproliferative process, could be monitored using the FDG-PET method.