Time course of metabolic activity and cellular infiltration in a murine model of acid-induced lung injury

This study investigates whether positron emission tomography (PET) can be used to monitor the inflammatory response and its correlation with the later fibroproliferative phase in an experimental model of acute lung injury. Hydrochloric acid (0.1 N, pH 1, 1.5 ml/kg) was instilled into the right bronchus of mice. A group of mice underwent a micro-computed tomography (CT) scan 1 h after lung injury and a series of 2-[F-18]fluorine-2-deoxy-d-glucose (FDG)-PET scans (6, 24 and 48 h and 7 days after surgery). After 21 days respiratory static compliance was assessed and lung tissue was collected in order to measure the hydroxy (OH)-proline content. Other groups of mice underwent micro-CT and micro-PET scans at the same time points, and then were immediately killed to assess arterial blood gases and histology. Histological analysis showed the recruitment of neutrophils and macrophages into the damaged lung, reaching the peak at 24 and 48 h, respectively. The time course of the [F-18]FDG signal, used as a marker of inflammation, correlated with that of recruited inflammatory cells. In mice killed 21 days after the surgery, a correlation was found between reduced respiratory static compliance and high PET signal 7 days after lung injury. The PET signal also correlated with the OH-proline content. This study demonstrated that PET imaging is a valid means of tracking the inflammatory response, also in longitudinal studies. Moreover, a correlation was found between persistence of the inflammatory response and fibrotic evolution of the injury.