title: Detection of subclinical synovitis with macrophage targeting and positron emission tomography in patients with rheumatoid arthritis without clinical arthritis.
abstract: OBJECTIVE
  To determine whether macrophage targeting by (R)-11C-PK11195 positron emission tomography (PET) can visualize subclinical joint inflammation in patients with rheumatoid arthritis (RA) without clinical arthritis during or after treatment, with flare as clinical outcome measure.
  
  
  METHODS
  (R)-11C-PK11195 PET and contrast-enhanced magnetic resonance imaging (MRI) of hands/wrists were performed in 29 patients with RA without clinical arthritis. (R)-11C-PK11195 PET uptake (semiquantitative score 0-3) in metacarpophalangeal, proximal interphalangeal, and wrist joints (i.e., 22 joints per patient) was scored and summed to obtain a cumulative PET score (range 0-66). Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) was performed on similar joints. Synovitis and bone marrow edema scores (>1) were summed to obtain a cumulative MRI score (range 0-288). Occurrence of flare was determined during 3-year followup.
  
  
  RESULTS
  Flare was observed in 17/29 patients (59%). (R)-11C-PK11195 PET showed enhanced tracer uptake in 16/29 patients (55%), of which 11 (69%) developed a flare. Highest cumulative PET scores (>6, n=3) corresponded with highest cumulative MRI scores (>39) and were related to development of flare in hands/wrists within 6 months. Cumulative PET scores of patients developing a flare were higher than those of patients without a flare [median (interquartile range) 2 (0-4.5) vs 0 (0-1), p<0.05]. In contrast, no significant differences were found between cumulative MRI scores of patients with and without a flare.
  
  
  CONCLUSIONS
  (R)-11C-PK11195 PET showed enhanced uptake, pointing to presence of subclinical synovitis in over half of patients without clinical arthritis. (R)-11C-PK11195 PET may be of value for prediction of exacerbation of RA, since cumulative PET scores > 1 were associated with development of flare within 3 years.
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade.
authors.forename: Yoony Y J
authors.initials: YY
authors.lastname: Gent
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Ahmadi
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade.
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade.
authors.forename: Nikie
authors.initials: N
authors.lastname: Hoetjes
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Kuijk
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade.
authors.forename: Karin
authors.initials: K
authors.lastname: Britsemmer
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade.
authors.forename: Franktien
authors.initials: F
authors.lastname: Turkstra
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade.
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade.
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.affiliation: From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade. j.vanderlaken@vumc.nl.
authors.forename: Conny J
authors.initials: CJ
authors.lastname: van der Laken
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000473:pathology*; D015331:Cohort Studies; D003287:Contrast Media; D018450:Disease Progression; D005260:Female; D005384:Finger Joint / Q000503:physiopathology; D005500:Follow-Up Studies; D006801:Humans; D007546:Isoquinolines; D008264:Macrophages / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013585:Synovitis / Q000000981:diagnostic imaging* / Q000473:pathology*; D014955:Wrist Joint / Q000503:physiopathology
chemical_list: D003287:Contrast Media; D007546:Isoquinolines; C037850:PK 11195
keywords: IMAGING; MACROPHAGE; POSITRON EMISSION TOMOGRAPHY; RHEUMATOID ARTHRITIS