2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography to Monitor Lung Inflammation and Therapeutic Response to Dexamethasone in a Murine Model of Acute Lung Injury
Tóm tắt
To image inflammation and monitor therapeutic response to anti-inflammatory intervention using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) in a preclinical model of acute lung injury (ALI). Mice were intratracheally administered lipopolysaccharide (LPS, 2.5 mg/kg) to induce ALI or phosphate-buffered saline as the vehicle control. A subset of mice in the ALI group received two intraperitoneal doses of dexamethasone 1 and 24 h after LPS. [18F]FDG PET/CT was performed 2 days after the induction of ALI. [18F]FDG uptake in the lungs was quantified by PET (%ID/mLmean and standardized uptake value (SUVmean)) and ex vivo γ-counting (%ID/g). The severity of lung inflammation was determined by quantifying the protein level of inflammatory cytokines/chemokines and the activity of neutrophil elastase and glycolytic enzymes. In separate groups of mice, flow cytometry was performed to estimate the contribution of individual immune cell types to the total pulmonary inflammatory cell burden under different treatment conditions. Lung uptake of [18F]FDG was significantly increased during LPS-induced ALI, and a decreased [18F]FDG uptake was observed following dexamethasone treatment to an intermediate level between that of LPS-treated and control mice. Protein expression of inflammatory biomarkers and the activity of neutrophil elastase and glycolytic enzymes were increased in the lungs of LPS-treated mice versus those of control mice, and correlated with [18F]FDG uptake. Furthermore, dexamethasone-induced decreases in cytokine/chemokine protein levels and enzyme activities correlated with [18F]FDG uptake. Neutrophils were the most abundant cells in LPS-induced ALI, and the pattern of total cell burden during ALI with or without dexamethasone therapy mirrored that of [18F]FDG uptake. [18F]FDG PET noninvasively detects lung inflammation in ALI and its response to anti-inflammatory therapy in a preclinical model. However, high [18F]FDG uptake by bone, brown fat, and myocardium remains a technical limitation for quantification of [18F]FDG in the lungs.
Tài liệu tham khảo
Matthay MA, Zemans RL, Zimmerman GA et al (2019) Acute respiratory distress syndrome. Nat Rev Dis Primers 5:18
Pham T, Rubenfeld GD (2017) Fifty years of research in ARDS. The epidemiology of acute respiratory distress syndrome. A 50th birthday review. Am J Respir Crit Care Med 195:860–870
Hendrickson KW, Peltan ID, Brown SM (2021) The epidemiology of acute respiratory distress syndrome before and after Coronavirus disease 2019. Crit Care Clin 37:703–716
Musch G, Venegas JG, Bellani G et al (2007) Regional gas exchange and cellular metabolic activity in ventilator-induced lung injury. Anesthesiology 106:723–735
Vass L, Fisk M, Lee S, Wilson FJ, Cheriyan J, Wilkinson I (2020) Advances in PET to assess pulmonary inflammation: a systematic review. Eur J Radiol 130:109182
Barreiro TJ, Perillo I (2004) An approach to interpreting spirometry. Am Fam Physician 69:1107–1114
Pauwels EK, McCready VR, Stoot JH, van Deurzen DF (1998) The mechanism of accumulation of tumour-localising radiopharmaceuticals. Eur J Nucl Med 25:277–305
Gallagher BM, Fowler JS, Gutterson NI, MacGregor RR, Wan CN, Wolf AP (1978) Metabolic trapping as a principle of oradiopharmaceutical design: some factors resposible for the biodistribution of [18F] 2-deoxy-2-fluoro-D-glucose. J Nucl Med 19:1154–1161
Barrio JR, Huang SC, Satyamurthy N et al (2020) Does 2-FDG PET accurately reflect quantitative in vivo glucose utilization? J Nucl Med 61:931–937
Chen DL, Schuster DP (2004) Positron emission tomography with [18F]fluorodeoxyglucose to evaluate neutrophil kinetics during acute lung injury. Am J Physiol Lung Cell Mol Physiol 286:L834-840
Chen DL, Rosenbluth DB, Mintun MA (1985) Schuster DP (2006) FDG-PET imaging of pulmonary inflammation in healthy volunteers after airway instillation of endotoxin. J Appl Physiol 100:1602–1609
Graebe M, Pedersen SF, Borgwardt L, Hojgaard L, Sillesen H, Kjaer A (2009) Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET). Eur J Vasc Endovasc Surg 37:714–721
O’Neill LA, Kishton RJ, Rathmell J (2016) A guide to immunometabolism for immunologists. Nat Rev Immunol 16:553–565
Chen DL, Bedient TJ, Kozlowski J et al (2009) [18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation. Am J Respir Crit Care Med 180:533–539
de Prost N, Tucci MR, Melo MF (2010) Assessment of lung inflammation with 18F-FDG PET during acute lung injury. AJR Am J Roentgenol 195:292–300
Capitanio S, Nordin AJ, Noraini AR, Rossetti C (2016) PET/CT in nononcological lung diseases: current applications and future perspectives. Eur Respir Rev 25:247–258
Subramanian DR, Jenkins L, Edgar R, Quraishi N, Stockley RA, Parr DG (2012) Assessment of pulmonary neutrophilic inflammation in emphysema by quantitative positron emission tomography. Am J Respir Crit Care Med 186:1125–1132
Torigian DA, Dam V, Chen X et al (2013) In vivo quantification of pulmonary inflammation in relation to emphysema severity via partial volume corrected (18)F-FDG-PET using computer-assisted analysis of diagnostic chest CT. Hell J Nucl Med 16:12–18
Jones HA, Marino PS, Shakur BH, Morrell NW (2003) In vivo assessment of lung inflammatory cell activity in patients with COPD and asthma. Eur Respir J 21:567–573
Yoon HY, Lee SH, Ha S, Ryu JS, Song JW (2021) The value of (18)F-FDG PET/CT in evaluating disease severity and prognosis in idiopathic pulmonary fibrosis patients. J Korean Med Sci 36:e257
Chen DL, Ferkol TW, Mintun MA, Pittman JE, Rosenbluth DB, Schuster DP (2006) Quantifying pulmonary inflammation in cystic fibrosis with positron emission tomography. Am J Respir Crit Care Med 173:1363–1369
Ishii T, Doi K, Okamoto K et al (2010) Neutrophil elastase contributes to acute lung injury induced by bilateral nephrectomy. Am J Pathol 177:1665–1673
Zhao Y, Olonisakin TF, Xiong Z et al (2015) Thrombospondin-1 restrains neutrophil granule serine protease function and regulates the innate immune response during Klebsiella pneumoniae infection. Mucosal Immunol 8:896–905
TeSlaa T, Teitell MA (2014) Techniques to monitor glycolysis. Methods Enzymol 542:91–114
Jelinek D, Flores A, Uebelhoer M et al (2018) Mapping metabolism: monitoring lactate dehydrogenase activity directly in tissue. J Vis Exp 136:e57760
Lokuta MA, Mehring GH, Paulnock DM (1997) Spectrophotometric determination of oxidative metabolism. Biotechniques 22:841–844
Chen DL, Ballout S, Chen L et al (2020) Consensus recommendations on the use of (18)F-FDG PET/CT in lung disease. J Nucl Med 61:1701–1707
Chen DL, Cheriyan J, Chilvers ER et al (2017) Quantification of lung PET images: challenges and opportunities. J Nucl Med 58:201–207
Soret M, Bacharach SL, Buvat I (2007) Partial-volume effect in PET tumor imaging. J Nucl Med 48:932–945
Carter LM, Kesner AL, Pratt EC et al (2020) The impact of positron range on PET resolution, evaluated with phantoms and PHITS monte carlo simulations for conventional and non-conventional radionuclides. Mol Imaging Biol 22:73–84
Kulkarni HS, Lee JS, Bastarache JA et al (2022) Update on the features and measurements of experimental acute lung injury in animals: an official American thoracic society workshop report. Am J Respir Cell Mol Biol 66:e1–e14
Bos LD, Schouten LR, van Vught LA et al (2017) Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis. Thorax 72:876–883
Famous KR, Delucchi K, Ware LB et al (2017) Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy. Am J Respir Crit Care Med 195:331–338
Reilly JP, Calfee CS, Christie JD (2019) Acute respiratory distress syndrome phenotypes. Semin Respir Crit Care Med 40:19–30
Williams AE, Chambers RC (2014) The mercurial nature of neutrophils: still an enigma in ARDS? Am J Physiol Lung Cell Mol Physiol 306:L217-230
Qu Y, Olonisakin T, Bain W et al (2018) Thrombospondin-1 protects against pathogen-induced lung injury by limiting extracellular matrix proteolysis. JCI Insight 3:e96914
Rodriguez-Prados JC, Traves PG, Cuenca J et al (2010) Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J Immunol 185:605–614
Borregaard N, Herlin T (1982) Energy metabolism of human neutrophils during phagocytosis. J Clin Investig 70:550–557
Sadiku P, Willson JA, Ryan EM et al (2021) Neutrophils fuel effective immune responses through gluconeogenesis and glycogenesis. Cell Metab 33(411–423):e414
Kelly B, O’Neill LA (2015) Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res 25:771–784
Tannahill GM, Curtis AM, Adamik J et al (2013) Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature 496:238–242
Beca JP, Scopes JW (1972) Serial determinations of blood lactate in respiratory distress syndrome. Arch Dis Child 47:550–557
Zhang H, Li Z, Zheng W et al (2022) Risk stratification of patients with acute respiratory distress syndrome complicated with sepsis using lactate trajectories. BMC Pulm Med 22:339
Wu C, Chen X, Cai Y et al (2020) Risk factors associated with acute respiratory distress syndrome and death in patients with Coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 180:934–943
Sipahioglu H, Onuk S (2022) Lactate dehydrogenase/albumin ratio as a prognostic factor in severe acute respiratory distress syndrome cases associated with COVID-19. Medicine (Baltimore) 101:e30759
Alipanah-Lechner N, Neyton L, Mick E et al (2023) Plasma metabolic profiling implicates dysregulated lipid metabolism and glycolytic shift in hyperinflammatory ARDS. Am J Physiol Lung Cell Mol Physiol 324:L297–L306
Santos AF, Povoa P, Paixao P, Mendonca A, Taborda-Barata L (2021) Changes in glycolytic pathway in SARS-COV 2 infection and their importance in understanding the severity of COVID-19. Front Chem 9:685196
Pourfathi M, Cereda M, Chatterjee S et al (2018) Lung metabolism and inflammation during mechanical ventilation. An Imaging Approach Sci Rep 8:3525
Robinson MJ, Krasnodembskaya AD (2020) Therapeutic targeting of metabolic alterations in acute respiratory distress syndrome. Eur Respir Rev 29:200114
Ledoult E, Morelle M, Soussan M et al (2021) (18)F-FDG positron emission tomography scanning in systemic sclerosis-associated interstitial lung disease: a pilot study. Arthritis Res Ther 23:76
Puuvuori E, Liggieri F, Velikyan I et al (2022) PET-CT imaging of pulmonary inflammation using [(68)Ga]Ga-DOTA-TATE. EJNMMI Res 12:19
Steinberg JD, Vogel W, Vegt E (2017) Factors influencing brown fat activation in FDG PET/CT: a retrospective analysis of 15,000+ cases. Br J Radiol 90:20170093
Long NM, Smith CS (2011) Causes and imaging features of false positives and false negatives on F-PET/CT in oncologic imaging. Insights Imaging 2:679–698
Keyes JW Jr (1995) SUV: standard uptake or silly useless value? J Nucl Med 36:1836–1839
Weiss GJ, Korn RL (2012) Interpretation of PET scans: do not take SUVs at face value. J Thorac Oncol 7:1744–1746
Blau M (1975) Letter: radiation dosimetry of 131-I-19-iodocholesterol: The pitfalls of using tissue concentration data. J Nucl Med 16:247–249
Adams MC, Turkington TG, Wilson JM, Wong TZ (2010) A systematic review of the factors affecting accuracy of SUV measurements. AJR Am J Roentgenol 195:310–320
Zambelli V, Di Grigoli G, Scanziani M et al (2012) Time course of metabolic activity and cellular infiltration in a murine model of acid-induced lung injury. Intensive Care Med 38:694–701
Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T (1992) Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 33:1972–1980
Liu Y, Gunsten SP, Sultan DH et al (2017) PET-based imaging of chemokine receptor 2 in experimental and disease-related lung inflammation. Radiology 283:758–768
Brody SL, Gunsten SP, Luehmann HP et al (2021) Chemokine receptor 2-targeted molecular imaging in pulmonary fibrosis. A clinical trial. Am J Respir Crit Care Med 203:78–89
Mannes PZ, Barnes CE, Biermann J et al (2023) Molecular imaging of chemokine-like receptor 1 (CMKLR1) in experimental acute lung injury. Proc Natl Acad Sci U S A 120:e2216458120
Haddad J, Latoche JD, Nigam S et al (2021) Molecular imaging of very late antigen-4 in acute lung injury. J Nucl Med 62:280–286
Cao Q, Huang Q, Mohan C, Li C (2019) Small-animal PET/CT imaging of local and systemic immune response using (64)Cu-alphaCD11b. J Nucl Med 60:1317–1324
Han W, Zaynagetdinov R, Yull FE et al (2015) Molecular imaging of folate receptor beta-positive macrophages during acute lung inflammation. Am J Respir Cell Mol Biol 53:50–59
Hardwick MJ, Chen MK, Baidoo K, Pomper MG, Guilarte TR (2005) In vivo imaging of peripheral benzodiazepine receptors in mouse lungs: a biomarker of inflammation. Mol Imaging 4:432–438
Antoni G, Lubberink M, Sorensen J et al (2023) In vivo visualization and quantification of neutrophil elastase in lungs of COVID-19 patients: a first-in-humans PET study with (11)C-NES. J Nucl Med 64:145–148