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

Purpose 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 [C-11](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. Material and methods 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 (BPND) were compared to lung macrophage presence, semi-quantified in pathology. Results The 3TCM was preferred in 142 lung regions (62%, 95% confidence interval: 56 to 69%). BPND 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 BPND (p = 0.03). Regional BPND 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). Conclusion To assess the intensity and spatial distribution of acute macrophagic lung inflammation in the context of experimental ARDS with mechanical ventilation, PET quantification of [C-11](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.

Automated summary

The study aimed to develop and validate a new lung inflammation imaging model and demonstrate through experimentation that this model can accurately quantify macrophagic inflammation while accounting for its non-specific and irreversible uptake in lung tissues. The results showed that the use of the new three-tissue compartment kinetic model significantly improved PET quantification in most lung regions.