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

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.