18F-FDG kinetics parameters depend on the mechanism of injury in early experimental acute respiratory distress syndrome

Abstract

PET with 18F-FDG allows for noninvasive assessment of regional lung metabolism reflective of neutrophilic inflammation. This study aimed at determining during early acute lung injury whether local 18F-FDG phosphorylation rate and volume of distribution were sensitive to the initial regional inflammatory response and whether they depended on the mechanism of injury: endotoxemia and surfactant depletion. Methods: Twelve sheep underwent homogeneous unilateral surfactant depletion (alveolar lavage) and were mechanically ventilated for 4 h (positive end-expiratory pressure, 10 cm H2O; plateau pressure, 30 cm H2O) while receiving intravenous endotoxin (lipopolysaccharide-positive [LPS1] group; n 5 6) or not (lipopolysaccharide-negative group; n 5 6). 18F-FDG PET emission scans were then acquired. 18F-FDG phosphorylation rate and distribution volume were calculated with a 4-compartment model. Lung tissue expression of inflammatory cytokines was measured using real-time quantitative reverse transcription polymerse chain reaction. Results: 18F-FDG uptake increased in LPS1 (P 5 0.012) and in surfactant-depleted sheep (P , 0.001). These increases were topographically heterogeneous, predominantly in dependent lung regions, and without interaction between alveolar lavage and LPS. The increase of 18F-FDGuptake in the LPS1groupwas related both to increases in the 18F-FDG phosphorylation rate (P , 0.05) and to distribution volume (P , 0.01). 18F-FDG distribution volume increased with infiltrating neutrophils (P,0.001) and phosphorylation ratewith the regional expression of IL-1β (P 5 0.026), IL-8 (P 5 0.011), and IL-10 (P 5 0.023). Conclusion: Noninvasive 18F-FDG PET-derived parameters represent histologic and gene expression markers of early lung injury. Pulmonary metabolism assessed with 18F-FDG PET depends on the mechanism of injury and appears to be additive for endotoxemia and surfactant depletion. 18F-FDG PET may be a valuable imaging biomarker of early lung injury.