[¹⁸F]Fluorodeoxyglucose Positron Emission Tomography for Lung Antiinflammatory Response Evaluation

Abstract

Rationale: 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. Objectives: To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutarylcoenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentallyinduced lung inflammation. Methods: 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. Measurements and Main 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 rhAPCtreated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC. Conclusions: 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).

Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

“…Animal studies have shown that neutrophils are primary effectors of ''atelectrauma,'' (9, 32) and, in the setting of pulmonary inflammation, PET is a sensitive tool to detect the activation of these cells. Microautoradiography studies conducted both in animals (2,5,19,33) and in humans (20,21,34) suggest that uptake of 18 FDG occurs primarily by neutrophils. Furthermore, neutrophil depletion profoundly blunts the injury induced by mechanical ventilation (35) and the uptake of 18 FDG, albeit without abolishing it (3,36).…”

“…Furthermore, neutrophil depletion profoundly blunts the injury induced by mechanical ventilation (35) and the uptake of 18 FDG, albeit without abolishing it (3,36). Because the remaining signal could possibly arise from lung parenchymal cells, PET with 18 FDG is considered to provide a ''global'' measure of inflammatory response of the lung (21). The capability of PET to detect atelectrauma has been directly investigated in at least two studies.…”

“…PET can detect the presence of metabolically active inflammatory cells, including neutrophils (2,3,5,(18)(19)(20)(21)(22), which have been shown to be primary effectors of VILI (3, 9, 10, 23-25). By combining PET…”

A View on Imaging in Drug Research and Development for Respiratory Diseases

“…18 F]FDG PET has been applied to demonstrate anti-inflammatory effects of statin treatment after endotoxin-induced lung inflammation in volunteers (Chen et al, 2009 Cu-labeled peptide that targets the formyl peptide receptor on neutrophils (Zhang et al, 2007;Locke et al, 2009) (Fig. 3).…”

Antisense peptide nucleic acid-functionalized cationic nanocomplex for in vivo mRNA detection

“…Reverse transcription was performed with the high-capacity cDNA reverse transcription kit (AB) in the presence of RNAse inhibitor (AB). The cDNA was then subjected to reverse transcription polymerase chain reaction (RT-PCR), using the [48] (370 kBq) was also used to evaluate the lung inflammation following the same endotoxin stimulation through biodistribution study with organs collected at 1 h p.i. [18].…”