title: Noninvasive imaging of macrophages in rheumatoid synovitis using 11C-(R)-PK11195 and positron emission tomography.
abstract: OBJECTIVE
  Noninvasive imaging by positron emission tomography (PET) of macrophages in inflamed joints of patients with rheumatoid arthritis (RA) may allow early detection of disease activity. We undertook this study to investigate whether rheumatoid synovitis can be visualized by PET using the tracer 11C-(R)-PK11195, which binds to peripheral benzodiazepine receptors (PBRs) on macrophages.
  
  
  METHODS
  Knee joints of 11 RA patients with active arthritis of at least 1 knee joint were imaged with 11C-(R)-PK11195 PET. Tissue uptake of 11C-(R)-PK11195 was quantified. PET was followed by arthroscopy of the most inflamed knee joint of each RA patient. Synovial tissue samples were subjected to immunohistochemical staining.
  
  
  RESULTS
  11C-(R)-PK11195 uptake on the PET scans was significantly higher in severely inflamed joints than in joints with moderate or mild signs of inflammation. In addition, tracer uptake in contralateral uninflamed knee joints of RA patients was significantly higher than in uninflamed joints of control patients without inflammatory joint disease, suggesting the presence of subclinical disease activity. PET tracer uptake in joints correlated significantly with PBR staining in the sublining of synovial tissue. PBR staining correlated significantly with CD68 staining of macrophages.
  
  
  CONCLUSIONS
  11C-(R)-PK11195 PET imaging allows noninvasive in vivo imaging of macrophages in rheumatoid synovitis and possibly even in subclinical synovitis. Noninvasive visualization of macrophages may be useful both for detecting early synovitis and for monitoring synovitis activity during treatment.
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands. j.vanderlaken@vumc.nl
authors.forename: Conny J
authors.initials: CJ
authors.lastname: van der Laken
authors.forename: Ernst H
authors.initials: EH
authors.lastname: Elzinga
authors.forename: Mark A
authors.initials: MA
authors.lastname: Kropholler
authors.forename: Carla F M
authors.initials: CF
authors.lastname: Molthoff
authors.forename: Joost W
authors.initials: JW
authors.lastname: van der Heijden
authors.forename: Kaoru
authors.initials: K
authors.lastname: Maruyama
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Ben A C
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging*; D001182:Arthroscopy; D001569:Benzodiazepines / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007546:Isoquinolines; D007719:Knee Joint; D008264:Macrophages / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011963:Receptors, GABA-A / Q000032:analysis; D013583:Synovial Membrane / Q000737:chemistry; D013585:Synovitis / Q000000981:diagnostic imaging*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001569:Benzodiazepines; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C037850:PK 11195