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

Abstract

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.

• Authors: Yoony Y J Gent, Alexandre E Voskuyl, Reina W Kloet, Dirkjan van Schaardenburg, Otto S Hoekstra, Ben A C Dijkmans, Adriaan A Lammertsma, Conny J van der Laken
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 64 Issue 1 Pg. 62-6 (Jan 2012) ISSN: 1529-0131 [Electronic] United States
• PMID: 21898356 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 by the American College of Rheumatology.

Chemical References

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

Topics

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