Local lung inflammation, assessed from 2-deoxy-2-[(18)F]fluoro-d-glucose (¹⁸F-FDG) kinetics parameters, demonstrated distinct temporal trajectories during early experimental acute respiratory distress syndrome. (A) The intensity and spatial heterogeneity of the ¹⁸F-FDG net uptake rate (K_i) increased with time. (A, B) During the first 6 h of injury, K_i increased significantly in all lung regions and heterogeneity of K_i became more pronounced than at baseline. From 6 to 20 h, K_i continued to increase only in nondependent and middle regions. Quantification of the determinants of ¹⁸F-FDG uptake (K_i = k₃⋅F_e; k₃ = phosphorylation rate; F_e = ¹⁸F-FDG volume of distribution) shows the compound nature of those local metabolic changes. (C) k₃ increased significantly in middle and dependent regions from 0 to 6 h followed by a rise in nondependent regions from 6 to 20 h. These findings indicate an acute early development of inflammation in middle and dependent lung regions, with subsequent activation in nondependent regions only after 6 h. (D) Increases in the distribution volume of ¹⁸F-FDG predominated in dependent regions, where they occurred throughout the experiment with larger magnitude, associated with lung derecruitment. *P < 0.05, **P < 0.01, and ***P < 0.001. ETX = endotoxemia; MV = mechanical ventilation.