Detection of subclinical synovitis with macrophage targeting and positron emission tomography in patients with rheumatoid arthritis without clinical arthritis

J Rheumatol. 2014 Nov;41(11):2145-52. doi: 10.3899/jrheum.140059. Epub 2014 Oct 1.

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.

Conclusion: (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.

Keywords: IMAGING; MACROPHAGE; POSITRON EMISSION TOMOGRAPHY; RHEUMATOID ARTHRITIS.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / diagnostic imaging*
  • Arthritis, Rheumatoid / pathology*
  • Cohort Studies
  • Contrast Media
  • Disease Progression
  • Female
  • Finger Joint / physiopathology
  • Follow-Up Studies
  • Humans
  • Isoquinolines
  • Macrophages / pathology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Prospective Studies
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Synovitis / diagnostic imaging*
  • Synovitis / pathology*
  • Wrist Joint / physiopathology

Substances

  • Contrast Media
  • Isoquinolines
  • PK 11195