PMID- 28237630 OWN - NLM STAT- MEDLINE DCOM- 20171128 LR - 20240213 IS - 1872-9614 (Electronic) IS - 0969-8051 (Print) IS - 0969-8051 (Linking) VI - 48 DP - 2017 May TI - (18)F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury. PG - 52-62 LID - S0969-8051(16)30318-3 [pii] LID - 10.1016/j.nucmedbio.2017.01.005 [doi] AB - 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 (18)F-fluoro-2-deoxyglucose ((18)F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of (18)F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for (14)C-2DG uptake in activated neutrophils. METHODS: Lung uptake of (18)F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/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 (14)C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. RESULTS: Significant uptake of (18)F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of (18)F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled (18)F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of (14)C-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 (18)F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of (14)C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: (18)F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate (14)C-2DG uptake in activated neutrophils. (18)F-FDG PET may provide a potential mechanism for early diagnosis and therapeutic assessment of ALI/ARDS. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Rodrigues, Rosana S AU - Rodrigues RS AD - Department of Radiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Bozza, Fernando A AU - Bozza FA AD - National Institute of Infectious Disease Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Hanrahan, Christopher J AU - Hanrahan CJ AD - Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Wang, Li-Ming AU - Wang LM AD - Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Wu, Qi AU - Wu Q AD - Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Hoffman, John M AU - Hoffman JM AD - Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Zimmerman, Guy A AU - Zimmerman GA AD - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - Morton, Kathryn A AU - Morton KA AD - Department of Radiology and Imaging Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA. Electronic address: kathryn.morton@hsc.utah.edu. LA - eng GR - R37 HL044525/HL/NHLBI NIH HHS/United States GR - U54 HL112311/HL/NHLBI NIH HHS/United States GR - UL1 TR001067/TR/NCATS NIH HHS/United States PT - Journal Article DEP - 20170117 PL - United States TA - Nucl Med Biol JT - Nuclear medicine and biology JID - 9304420 RN - 0 (Glucose Transport Proteins, Facilitative) RN - 0 (Lipopolysaccharides) RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) RN - EC 2.7.1.1 (Hexokinase) SB - IM MH - Acute Lung Injury/chemically induced/*diagnostic imaging/*immunology/metabolism MH - Animals MH - Biological Transport/drug effects MH - Cell Membrane/drug effects/metabolism MH - Cytosol/drug effects/metabolism MH - *Fluorodeoxyglucose F18/metabolism MH - Gene Expression Regulation, Enzymologic/drug effects MH - Glucose Transport Proteins, Facilitative/metabolism MH - Hexokinase/metabolism MH - Lipopolysaccharides/*pharmacology MH - Lung/diagnostic imaging/drug effects/immunology/pathology MH - Male MH - Neutrophil Activation/*drug effects MH - Neutrophils/cytology/*drug effects/immunology MH - *Positron-Emission Tomography MH - Rats MH - Rats, Sprague-Dawley MH - Respiratory Distress Syndrome/chemically induced/diagnostic imaging/immunology/metabolism PMC - PMC5380510 MID - NIHMS844203 OTO - NOTNLM OT - 18F-fluordeoxyglucose OT - ARDS OT - Acute lung injury OT - FDG OT - Lipopolysaccharide OT - Neutrophils EDAT- 2017/02/27 06:00 MHDA- 2017/11/29 06:00 PMCR- 2018/05/01 CRDT- 2017/02/27 06:00 PHST- 2016/10/14 00:00 [received] PHST- 2016/12/10 00:00 [revised] PHST- 2017/01/12 00:00 [accepted] PHST- 2017/02/27 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/02/27 06:00 [entrez] PHST- 2018/05/01 00:00 [pmc-release] AID - S0969-8051(16)30318-3 [pii] AID - 10.1016/j.nucmedbio.2017.01.005 [doi] PST - ppublish SO - Nucl Med Biol. 2017 May;48:52-62. doi: 10.1016/j.nucmedbio.2017.01.005. Epub 2017 Jan 17.