PET imaging of lung inflammation with [18F]FEDAC, a radioligand for translocator protein (18 kDa)

PLoS One. 2012;7(9):e45065. doi: 10.1371/journal.pone.0045065. Epub 2012 Sep 12.

Abstract

Purpose: The translocator protein (18 kDa) (TSPO) is highly expressed on the bronchial and bronchiole epithelium, submucosal glands in intrapulmonary bronchi, pneumocytes and alveolar macrophages in human lung. This study aimed to perform positron emission tomography (PET) imaging of lung inflammation with [(18)F]FEDAC, a specific TSPO radioligand, and to determine cellular sources enriching TSPO expression in the lung.

Methods: An acute lung injury model was prepared by intratracheal administration of lipopolysaccharide (LPS) to rat. Uptake of radioactivity in the rat lungs was measured with small-animal PET after injection of [(18)F]FEDAC. Presence of TSPO was examined in the lung tissue using Western blot and immunohistochemical assays.

Results: The uptake of [(18)F]FEDAC increased in the lung with the progress of inflammation by treatment with LPS. Pretreatment with a TSPO-selective ligand PK11195 showed a significant decrease in the lung uptake of [(18)F]FEDAC due to competitive binding to TSPO. TSPO expression was elevated in the inflamed lung section and its level responded to the [(18)F]FEDAC uptake and severity of inflammation. Increase of TSPO expression was mainly found in the neutrophils and macrophages of inflamed lungs.

Conclusion: From this study we conclude that PET with [(18)F]FEDAC may be a useful tool for imaging TSPO expression and evaluating progress of lung inflammation. Study on human lung using [(18)F]FEDAC-PET is promising.

MeSH terms

  • Acetamides* / pharmacokinetics
  • Animals
  • Area Under Curve
  • Blotting, Western
  • Carbon Radioisotopes / pharmacokinetics
  • Carrier Proteins / metabolism*
  • Fluorescent Antibody Technique
  • Fluorine Radioisotopes / pharmacokinetics
  • Isoquinolines / pharmacokinetics
  • Ligands
  • Lipopolysaccharides / pharmacology
  • Lung / diagnostic imaging
  • Lung / metabolism
  • Lung / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Pneumonia / diagnosis*
  • Positron-Emission Tomography / methods*
  • Pulmonary Alveoli / diagnostic imaging
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / pathology
  • Purines* / pharmacokinetics
  • Radiopharmaceuticals* / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism*
  • Tissue Distribution / drug effects

Substances

  • Acetamides
  • Carbon Radioisotopes
  • Carrier Proteins
  • Fluorine Radioisotopes
  • Isoquinolines
  • Ligands
  • Lipopolysaccharides
  • N-benzyl-N-methyl-2-(7,8-dihydro-7-(2-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl)acetamide
  • Purines
  • Radiopharmaceuticals
  • Receptors, GABA-A
  • Tspo protein, rat
  • PK 11195

Grant support

The authors have no support or funding to report.