RT Journal Article
SR Electronic
T1 PET imaging with [<sup>11</sup>C]PBR28 and [<sup>18</sup>F]FDG distinguishes macrophage from neutrophil lung inflammation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P1693
VO 40
IS Suppl 56
A1 Chen, Delphine
A1 Agapov, Eugene
A1 Solingapuram, Kiran
A1 Engle, Jacquelyn
A1 Griffin, Elizabeth
A1 Brody, Steven
A1 Woods, Jason
A1 Mach, Robert
A1 Pierce, Richard
A1 Holtzman, Michael
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P1693.abstract
AB Introduction: Noninvasive methods for quantifying macrophage and neutrophil activation and recruitment in chronic obstructive pulmonary disease (COPD) would be highly useful in assessing the efficacy of anti-inflammatory therapies.Objective: To test whether positron emission tomography (PET) imaging with [11C]PBR28 and [18F]fluorodeoxyglucose ([18F]FDG) could distinguish macrophage-dominant from neutrophilic inflammation in a mouse model of COPD.Methods: C57BL/6J mice inoculated with PBS or Sendai virus were imaged by microPET (Inveon or Focus 220, Siemens/CTI) with both [11C]PBR28 and [18F]FDG at Days 3 and 84 post-inoculation (p.i.). Regions of interest placed over the lungs determined the % injected dose per cc (%ID/cc) at 60 min. Lung sections were stained for TSPO ([11C]PBR28 ligand), Ly6G (neutrophil marker) and CD68 (macrophage marker).Results: Only [18F]FDG uptake increased significantly during acute illness at p.i. Day 3. Both [11C]PBR28 and [18F]FDG uptake increased significantly during chronic disease at p.i. Day 84. The [11C]PBR28:[18F]FDG ratio, calculated for each mouse, was no different between infected (1.9 ± 0.3) and uninfected mice (2.0 ± 0.4) at p.i. Day 3. This ratio increased significantly at p.i. Day 84 (3.1 ± 0.9) in infected mice compared to controls (1.7 ± 0.5). Lung sections showed macrophages with intense TSPO staining at p.i. Day 84.Conclusion: PET imaging with [11C]PBR28 and [18F]FDG quantitatively distinguishes macrophage-dominant from neutrophilic inflammation in a mouse model of COPD. This approach may be useful for monitoring the pulmonary macrophage burden in humans with COPD, thereby guiding emerging targeted anti-inflammatory therapies.