Background/Purpose:

Macrophages play an important role in the pathophysiology of Rheumatoid Arthritis (RA). Targeting of macrophages by (R)-[¹¹C]PK11195 positron emission tomography (PET) has previously been successfully used for imaging of (subclinical) synovitis in preclinical and established RA patients. It is known that a considerable number of RA patients with minimal disease activity or remission may have subclinical disease activity as well. Therefore, we have performed a prospective pilot study in which (R)-[¹¹C]PK11195 PET was used to visualise subclinical inflammation in hand and/or wrist joints of RA patients that are in DAS28 clinical remission, in relation to magnetic resonance imaging (MRI) at baseline and clinical outcome within 3 years.

Methods:

High spatial resolution (R)-[¹¹C]PK11195 PET scans and contrast-enhanced MRI scans of both hands and wrists were performed in twenty-nine RA patients without any signs of arthritis according a 28-joint count and fulfilling DAS28 clinical remission. PET tracer uptake was scored semiquantitatively according a 0-3 scale and MRI scans were scored for presence of synovitis and bone marrow edema (BME) according to the OMERACT RAMRIS score. Cumulative scores were calculated by adding up joint scores of all metacarpophalangeal, proximal interphalangeal and wrist joints (range PET 0-66; range MRI 0-222). 

Results:

(R)-[¹¹C]PK11195 PET scans showed evidence of subclinical arthritis in at least one  hand and/or wrist joint in 16/29 (55%) of patients. Flare of clinical arthritis was found in 17/29 (59%) of patients within 3 years of clinical follow-up. Patients with cumulative PET scores >6 (n=3) and scores of 4-5 (n=2) developed arthritis in hands/wrists within respectively 26 weeks and 52 weeks. Patients with high cumulative PET scores of >6 also depicted high cumulative MRI scores of >37. In patients without flare of clinical arthritis within 3 years (n=12), PET scores were always low or negative (≤1), but MRI scores varied between 0 and 27. 

Conclusion:

This prospective pilot study shows that macrophage targeting by (R)-[¹¹C]PK11195 PET visualises subclinical synovitis in hand/wrist joints of RA patients in DAS28 remission. At patient level, high cumulative PET scores may predict a short-term flare of arthritis activity. (R)-[¹¹C]PK11195 PET may be of additive value to MRI for detection of subclinical synovitis in DAS28 remission patients, in particular with regard to specificity, but this needs to be confirmed in larger patient cohorts.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/subclinical-arthritis-visualised-by-positron-emission-tomography-and-macrophage-targeting-precedes-clinical-flare-in-rheumatoid-arthritis-patients-in-das28-remission/