Non-invasive quantification of acute macrophagic lung inflammation with [¹¹C](R)-PK11195 using a three-tissue compartment kinetic model in experimental acute respiratory distress syndrome.

Abstract

Imaging of acute lung inflammation is pivotal to evaluate innovative ventilation strategies. We aimed to develop and validate a three-tissue compartment kinetic model (3TCM) of [¹¹C](R)-PK11195 lung uptake in experimental acute respiratory distress syndrome (ARDS) to help quantify macrophagic inflammation, while accounting for the impact of its non-specific and irreversible uptake in lung tissues. We analyzed the data of 38 positron emission tomography (PET) studies performed in 21 swine with or without experimental ARDS, receiving general anesthesia and mechanical ventilation. Model input function was a plasma, metabolite-corrected, image-derived input function measured in the main pulmonary artery. Regional lung analysis consisted in applying both the 3TCM and the two-tissue compartment model (2TCM); in each region, the best model was selected using a selection algorithm with a goodness-of-fit criterion. Regional best model binding potentials (BP_ND) were compared to lung macrophage presence, semi-quantified in pathology. The 3TCM was preferred in 142 lung regions (62%, 95% confidence interval: 56 to 69%). BP_ND determined by the 2TCM was significantly higher than the value computed with the 3TCM (overall median with interquartile range: 0.81 [0.44-1.33] vs. 0.60 [0.34-0.94], p < 0.02). Regional macrophage score was significantly associated with the best model BP_ND (p = 0.03). Regional BP_ND was significantly increased in the hyperinflated lung compartment, compared to the normally aerated one (median with interquartile range: 0.8 [0.6-1.7] vs. 0.6 [0.3-0.8], p = 0.03). To assess the intensity and spatial distribution of acute macrophagic lung inflammation in the context of experimental ARDS with mechanical ventilation, PET quantification of [¹¹C](R)-PK11195 lung uptake was significantly improved in most lung regions using the 3TCM. This new methodology offers the opportunity to non-invasively evaluate innovative ventilatory strategies aiming at controlling acute lung inflammation.