Macrophage positron emission tomography imaging as a biomarker for preclinical rheumatoid arthritis: findings of a prospective pilot study

Arthritis Rheum. 2012 Jan;64(1):62-6. doi: 10.1002/art.30655.


Objective: To conduct a prospective pilot study to determine whether macrophage targeting by 11C-(R)-PK11195 positron emission tomography (PET) can visualize subclinical synovitis in arthralgia patients who have anti-citrullinated protein antibodies (ACPAs).

Methods: Twenty-nine arthralgia patients who were positive for ACPAs but did not have clinical arthritis were studied. High (spatial)-resolution 11C-(R)-PK11195 PET scans of the hands and wrists were performed. For all metacarpophalangeal, proximal interphalangeal, and wrist joints (i.e., 22 joints per patient), tracer uptake was scored semiquantitatively (0-3 scale) by 2 observers who were blinded with regard to the clinical data. Patients were followed up prospectively for 24 months to investigate the development of clinical arthritis.

Results: Overall agreement and kappa values for the readings of the 2 observers were, respectively, 97% and 0.91 (95% confidence interval [95% CI] 0.74-1) at the patient level and 99% and 0.81 (95% CI 0.65-0.96) at the joint level. In 4 patients, at least 1 and as many as 5 PET-positive joints (score≥1) were found at baseline. Within 2 years of followup, 9 patients had developed clinical arthritis. This included all 4 patients with positive findings on the 11C-(R)-PK11195 scan, who developed clinical arthritis in the hand/wrist region, as identified on PET scans. Of the 5 remaining arthritis patients with negative findings on PET scans, 2 developed arthritis in the hand joints and 3 developed arthritis at locations outside the field of view of the PET scanner.

Conclusion: Subclinical arthritis in ACPA-positive arthralgia patients could be visualized by 11C-(R)-PK11195 PET scanning and was associated with development of arthritis within 2 years of followup. This indicates that 11C-(R)-PK11195 PET may be useful in determining arthritis activity in the preclinical phase of RA.

MeSH terms

  • Adult
  • Amides
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnostic imaging*
  • Arthritis, Rheumatoid / immunology
  • Female
  • Humans
  • Isoquinolines
  • Macrophages / diagnostic imaging*
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Observer Variation
  • Peptides, Cyclic / blood
  • Peptides, Cyclic / immunology
  • Pilot Projects
  • Positron-Emission Tomography / methods*
  • Prospective Studies
  • Radiopharmaceuticals
  • Synovitis / blood
  • Synovitis / diagnostic imaging*
  • Synovitis / immunology


  • (R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide
  • Amides
  • Isoquinolines
  • Peptides, Cyclic
  • Radiopharmaceuticals
  • cyclic citrullinated peptide