18 F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury

Abstract

Introduction Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18F-fluoro-2-deoxyglucose (18F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14C-2DG uptake in activated neutrophils. Methods Lung uptake of 18F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24 hours following the intraperitoneal injection of 10 mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Results Significant uptake of 18F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Conclusion Systemic endotoxin-induced ALI results in very early and progressive uptake of 18F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. Advances in knowledge and implications for patient care 18F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14C-2DG uptake in activated neutrophils. 18F-FDG PET may provide a potential mechanism for early diagnosis and therapeutic assessment of ALI/ARDS.

Close down the lungs and keep them resting to minimize ventilator-induced lung injury

“…In fact, pulmonary FDG kinetics are altered during both experimental and clinical ARDS. Therefore, FDG-PET has been proposed as a potential non-invasive method to provide comprehensive understanding of the mechanisms of ARDS, and help for early diagnosis and for evaluation of different therapeutic interventions [ 28 ]. Other techniques used PET with a sialic acid-binding immunoglobulin-like lectin 9 (siglec-9)-based imaging agent targeting vascular adhesion protein-1 (VAP-1) for quantification of regional pulmonary inflammation [ 29 ].…”

Quantification of Regional Murine Ozone-Induced Lung Inflammation Using [18F]FDG MicroPET/CT Imaging

“…]FDG-PET signal correlates with the presence of activated neutrophils(6). Clinical studies have also demonstrated that [ 18 F]FDG-PET imaging can be used to assess the neutrophilic inflammatory burden in the lungs in cystic fibrosis, pneumonia, and experimentally induced lung inflammation(6)(7)(8)(9). These results together indicate that [ 18 F]FDG-PET imaging can potentially be used to measure changes in pulmonary inflammation in response to anti-inflammatory treatments.We set out to explore 2 questions:(1) the utility of dynamic [ 18 F]FDG-PET acquisition in discriminating before and after O 3 exposure; (2) the feasibility of [ 18 F]FDG-PET in tracking the pathology of O 3 induced lung inflammation in in vivo O 3 models and their response over time (0, 24 and 28 h).…”

“…]FDG-PET signal correlates with the presence of activated neutrophils(6). Clinical studies have also demonstrated that [ 18 F]FDG-PET imaging can be used to assess the neutrophilic inflammatory burden in the lungs in cystic fibrosis, pneumonia, and experimentally induced lung inflammation(6)(7)(8)(9).…”

Analysis of retention of gadolinium by brain, bone, and blood following linear gadolinium‐based contrast agent administration in rats with experimental sepsis

“…At 24 hours following GBCA injection, the blood content of Gd in LPS‐treated rats was approximately 44.7% higher than in control rats, although this difference was not significant. We have shown that a single high dose of LPS to rats results in multiple effects seen in septic patients, including pulmonary and neuroinflammation . It is possible that some degree of acute renal injury in the LPS‐treated rats during the first 24 hours after contrast injection could have resulted in higher GBCA levels in the blood and delivery to the brain, which may have normalized by 24 hours.…”