PT - JOURNAL ARTICLE AU - de Prost, Nicolas AU - Feng, Yan AU - Wellman, Tyler AU - Tucci, Mauro R. AU - Costa, Eduardo L. AU - Musch, Guido AU - Winkler, Tilo AU - Harris, R. Scott AU - Venegas, Jose G. AU - Chao, Wei AU - Vidal Melo, Marcos F. TI - <sup>18</sup>F-FDG Kinetics Parameters Depend on the Mechanism of Injury in Early Experimental Acute Respiratory Distress Syndrome AID - 10.2967/jnumed.114.140962 DP - 2014 Nov 01 TA - Journal of Nuclear Medicine PG - 1871--1877 VI - 55 IP - 11 4099 - http://jnm.snmjournals.org/content/55/11/1871.short 4100 - http://jnm.snmjournals.org/content/55/11/1871.full SO - J Nucl Med2014 Nov 01; 55 AB - 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 [LPS+] group; n = 6) or not (lipopolysaccharide-negative group; n = 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 polymerase chain reaction. Results: 18F-FDG uptake increased in LPS+ (P = 0.012) and in surfactant-depleted sheep (P &lt; 0.001). These increases were topographically heterogeneous, predominantly in dependent lung regions, and without interaction between alveolar lavage and LPS. The increase of 18F-FDG uptake in the LPS+ group was related both to increases in the 18F-FDG phosphorylation rate (P &lt; 0.05) and to distribution volume (P &lt; 0.01). 18F-FDG distribution volume increased with infiltrating neutrophils (P &lt; 0.001) and phosphorylation rate with the regional expression of IL-1β (P = 0.026), IL-8 (P = 0.011), and IL-10 (P = 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.