| Title | [18F] fluorodeoxyglucose Positron Emission Tomography for Lung Anti-inflammatory Response Evaluation. | | Author(s) | Chen DL, Bedient TJ, Kozlowski J, Rosenbluth DB, Isakow W, Ferkol TW, Thomas B, Mintun MA, Schuster DP, Walter MJ | | Institution | Mallinckrodt Institue of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States. | | Source | Am J Respir Crit Care Med 2009 Jul 2. | | Abstract | RATIONALE: Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to anti-inflammatory treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation.
OBJECTIVE: To evaluate the ability of FDG-PET to measure the pulmonary anti-inflammatory effects of hydroxymethyl-glutaryl coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced 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 Ki 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 Ki 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 Ki was observed in the rhAPC-treated group correlating with a lack of change in BAL parameters, indicating no significant anti-inflammatory effect with rhAPC.
CONCLUSION: FDG-PET imaging is a sensitive method for quantifying the lung-specific response to anti-inflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel anti-inflammatory therapies at early phases in the drug development process. Clinical Trial Registry Information: ID# NCT00741013 at www.clinicaltrials.gov. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19574441 |
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