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[18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation.

ABSTRACT: Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation.To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced lung inflammation.Eighteen healthy volunteers were randomized to receive placebo, lovastatin, or rhAPC before intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed before and after endotoxin instillation. The rate of [(18)F]FDG uptake was calculated as the influx constant K(i) by Patlak graphical analysis. Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations for correlation with the PET imaging results.There was a statistically significant decrease in K(i) in the lovastatin-treated group that was not seen in the placebo-treated group, suggesting attenuation of inflammation by lovastatin treatment despite a small decrease in BAL total leukocyte and neutrophil counts that was not statistically significant. No significant decrease in K(i) was observed in the rhAPC-treated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC.FDG-PET imaging is a sensitive method for quantifying the lung-specific response to antiinflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel antiinflammatory therapies at early phases in the drug development process. Clinical trial registered with www.clinicaltrials.gov (NCT00741013).

SUBMITTER: Chen DL

PROVIDER: S-EPMC2742744 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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[18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation.

Chen Delphine L DL Bedient Timothy J TJ Kozlowski James J Rosenbluth Daniel B DB Isakow Warren W Ferkol Thomas W TW Thomas Betsy B Mintun Mark A MA Schuster Daniel P DP Walter Michael J MJ

American journal of respiratory and critical care medicine 20090702 6

<h4>Rationale</h4>Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation.<h4>Objectives</h4>To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statin ...[more]

PMID: 19574441

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Project description:Positron emission tomography (PET) visualizes increased cellular [F]fluorodeoxyglucose ([F]FDG) uptake. Pulmonary hypertension (PH) is conceived of a proliferative disease of the lung vessels. Increased glucose uptake can be quantified as pulmonary [F]FDG uptake via PET imaging. Because the angioproliferative mechanisms in PH are still in need of further description, the aim of the present study was to investigate whether [F]FDG PET/CT imaging can elucidate these pathophysiologic mechanisms in different etiologies of PH.Patients (n?=?109) with end-stage pulmonary disease being evaluated for lung transplant were included in this observational study. Mean standardized uptake value (SUVmean) of predefined regions of interest in lung parenchyma (LP), left (LV), and right ventricle (RV) of the heart, and SUVmax in pulmonary artery (PA) were determined and normalized to liver uptake. These SUV ratios (SUVRs) were compared with results from right heart catheterization (mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR]), and serum N-terminal pro-brain natriuretic peptide. Group comparisons were performed and Pearson correlation coefficients (r) were calculated.The [F]FDG uptake ratios in LP, RV, RV/LV, and PA, but not in LV, were found to be significantly higher in both patients with mPAP ?25?mm Hg (P?=?0.013, P?=?0.006, P?=?0.049, P?=?0.002, P?=?0.68, respectively) and with PVR ?480?dyn·s/cm (P?<?0.001, P?=?0.045, P?<?0.001, P?<?0.001, P?=?0.26, respectively). The [F]FDG uptake in these regions positively correlated also with mPAP, PVR, and N-terminal pro-brain natriuretic peptide. The SUVR of PA positively correlated with the SUVR of LP and RV (r?=?0.55, r?=?0.42, respectively).Pulmonary and cardiac [F]FDG uptake in PET imaging positively correlated with the presence and severity of PH in patients with end-stage pulmonary disease. Increased glucose metabolism in the central PAs seems to play a certain role in terms of severity of PH. These results suggest that [F]FDG-PET imaging can help understand the pathophysiology of PH as a proliferative pulmonary disease.

Project description:COPD and smoking are characterised by pulmonary inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker. To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in "usual" (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients. Data from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKi and systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKi values at baseline and at 4-month follow-up. COPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001 versus 0.0028±0.001 mL·cm-3·min-1, respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi (β=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory volume in 1 s % predicted, systemic neutrophils and C-reactive protein levels. Mean percentage difference in nKi between the baseline and follow-up was 3.2%, and the within subject coefficient of variability was 7.7%. FDG PET/CT has potential as a noninvasive tool to enable whole lung and regional quantification of FDG uptake to assess smoking- and COPD-related pulmonary inflammation.

Project description:Purpose: To investigate the correlation between 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters and clinicopathological factors in pathological subtypes of invasive lung adenocarcinoma and prognosis. Patients and Methods: Metabolic parameters and clinicopathological factors from 176 consecutive patients with invasive lung adenocarcinoma between August 2008 and August 2016 who underwent 18F-FDG PET/CT examination were retrospectively analyzed. Invasive lung adenocarcinoma was divided into five pathological subtypes:lepidic predominant adenocarcinoma (LPA), acinar predominant adenocarcinoma (APA), papillary predominant adenocarcinoma (PPA), solid predominant adenocarcinoma (SPA), and micropapillary predominant adenocarcinoma (MPA). The differences in metabolic parameters [maximal standard uptake value (SUVmax), mean standard uptake value (SUVmean), total lesion glycolysis (TLG), and metabolic tumor volume (MTV)] and tumor diameter for different pathological subtypes were analyzed. Patients were divided into two groups according to their prognosis: good prognosis group (LPA, APA, PPA) and poor prognosis group (SPA, MPA). Logistic regression was used to filter predictors and construct a predictive model, and areas under the receiver operating curve (AUC) were calculated. Cox regression analysis was performed on prognostic factors. Results: 82 (46.6%) females and 94 (53.4%) males of patients with invasive lung adenocarcinoma were enrolled in this study. Metabolic parameters and tumor diameter of different pathological subtype had statistically significant (P < 0.05). The predictive model constructed using independent predictors (Distant metastasis, Ki-67, and SUVmax) had good classification performance for both groups. The AUC for SUVmax was 0.694 and combined with clinicopathological factors were 0.745. Cox regression analysis revealed that Stage, TTF-1, MTV, and pathological subtype were independent risk factors for patient prognosis. The hazard ratio (HR) of the poor prognosis group was 1.948 (95% CI 1.042-3.641) times the good prognosis group. The mean survival times of good and poor prognosis group were 50.2621 (95% CI 47.818-52.706) and 35.8214 (95% CI 27.483-44.159) months, respectively, while the median survival time was 47.00 (95% CI 45.000-50.000) and 31.50 (95% CI 23.000-49.000) months, respectively. Conclusion: PET/CT metabolic parameters combined with clinicopathological factors had good classification performance for the different pathological subtypes, which may provide a reference for treatment strategies and prognosis evaluation of patients.

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[18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation.

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[18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation.

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