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


OBJECTIVE
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 [(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.


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).
Chen
Delphine L
DL
Mallinckrodt Institute of Radiology, Division of Nuclear Medicine, Campus Box 8223, 510 S. Kingshighway Blvd., St. Louis, MO 63110, USA. chend@mir.wustl.edu
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
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008148:Lovastatin / Q000627:therapeutic use; D008297:Male; D018375:Neutrophil Activation; D011014:Pneumonia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000276:immunology; D049268:Positron-Emission Tomography / Q000379:methods; D011486:Protein C / Q000627:therapeutic use; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins / Q000627:therapeutic use; D055815:Young Adult
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011486:Protein C; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D019788:Fluorodeoxyglucose F18; D008148:Lovastatin