title: Imaging of carrageenan-induced local inflammation and adjuvant-induced systemic arthritis with [(11)C]PBR28 PET.
abstract: BACKGROUND
  [(11)C] PBR28 binding to translocator protein (TSPO) was evaluated for imaging of acute and chronic inflammation using two established rat models.
  
  
  METHODS
  Acute inflammation was induced by local carrageenan injection into the paw of Fisher 344 rats (model A). T-cell mediated adjuvant arthritis was induced by heat-inactivated Mycobacterium butyricum injection in Lewis rats (model B). Micro-PET scan was performed after injection of approximately 35 MBq [(11)C]PBR28. In model A, volumes of interest (VOIs) were defined in the paw of Fisher 344 rats (n=6) with contralateral sham treatment as control. For model B, VOIs were defined in the tail, sacroiliac joints, hips, knees and thigh muscles of M. butyricum treated animals (n=8) and compared with sham-treated controls (n=4). The peak (11)C-PBR28 SUV (SUVpeak) and area under the curve (AUCSUV) of 60-minute time-activity data were calculated. Immunohistochemistry for CD68, a macrophage stain, was performed from paw tissues. In addition, the [(11)C]PBR28 cell uptake was measured in lipopolysaccharide (LPS)-stimulated and non-stimulated macrophage cultures.
  
  
  RESULTS
  LPS-stimulated macrophages displayed dose-dependent increased [(11)C]PBR28 uptake, which was blocked by non-labeled PBR28. In both models, radiotracer uptake of treated lesions increased rapidly within minutes and displayed overall accumulative kinetics. The SUVpeak and AUCSUV of carrageenan-treated paws was significantly increased compared to controls. Also, the [(11)C]PBR28 uptake ratio of carrageenan-treated vs. sham-treated paw correlated significantly with CD68 staining ratios of the same animals. In adjuvant arthritis, significantly increased [(11)C]PBR28 SUVpeak and AUCSUV values were identified at the tail, knees, and sacroiliac joints, while no significant differences were identified in the lumbar spine and hips.
  
  
  CONCLUSIONS
  Based on our initial data, [(11)C]PBR28 PET appears to have potential for imaging of various inflammatory processes involving macrophage activation.
authors.affiliation: Department of Radiology, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Shao
authors.forename: Xueding
authors.initials: X
authors.lastname: Wang
authors.forename: Sean J
authors.initials: SJ
authors.lastname: English
authors.forename: Timothy
authors.initials: T
authors.lastname: Desmond
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Sherman
authors.forename: Carole A
authors.initials: CA
authors.lastname: Quesada
authors.forename: Morand R
authors.initials: MR
authors.lastname: Piert
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology; D001692:Biological Transport; D002351:Carrageenan / Q000009:adverse effects*; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D049268:Positron-Emission Tomography; D011743:Pyrimidines / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats
chemical_list: C526315:(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; D011743:Pyrimidines; D002351:Carrageenan
keywords: Carrageenan-induced inflammation macrophages, RAW 264.7 cells; Systemic adjuvant arthritis; TSPO; [(11)C]PBR28
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