title: In vivo imaging of peripheral benzodiazepine receptors in mouse lungs: a biomarker of inflammation.
abstract: The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [(123)I]-(R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals (p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [(11)C]-(R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.
authors.affiliation: Loyola College, Baltimore, MD, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hardwick
authors.forename: Ming-Kai
authors.initials: MK
authors.lastname: Chen
authors.forename: Kwamena
authors.initials: K
authors.lastname: Baidoo
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.forename: Tomás R
authors.initials: TR
authors.lastname: Guilarte
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D002250:Carbon Radioisotopes; D007249:Inflammation / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography; D018079:Receptors, GABA / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C463819:Bzrp protein, mouse; D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D018079:Receptors, GABA