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

Delphine L. Chen¹, Timothy J. Bedient², James Kozlowski¹, Daniel B. Rosenbluth², Warren Isakow², Thomas W. Ferkol³, Betsy Thomas¹, Mark A. Mintun¹, Daniel P. Schuster^1,2, and Michael J. Walter^2,3

¹ Mallinckrodt Institute of Radiology, ² Department of Internal Medicine, and ³ Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri

Correspondence and requests for reprints should be addressed to Delphine L. Chen, M.D., Mallinckrodt Institute of Radiology, Division of Nuclear Medicine, Campus Box 8223, 510 S. Kingshighway Blvd., St. Louis, MO 63110. E-mail: chend{at}mir.wustl.edu

Rationale: Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [¹⁸F]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 hydroxymethylglutaryl-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 [¹⁸F]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 rhAPC-treated 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).

Key Words: lovastatin • neutrophils • drug development • biomarker

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Noninvasive tests that can accurately quantify lung-specific antiinflammatory properties of therapeutic agents are currently not available. Positron emission tomographic (PET) imaging with [18F]fluorodeoxyglucose (FDG-PET) is a sensitive, noninvasive method for quantifying neutrophilic pulmonary inflammation. What This Study Adds to the Field We show that FDG-PET can detect changes in levels of pulmonary inflammation, and also provide evidence of the antiinflammatory properties of lovastatin.