Rheumatoid arthritis (RA) is a chronic, inflammatory disease that affects the joints. RA patients with high levels of disease activity have worse clinical and radiological outcomes than patients with minimal disease activity (MDA) or patients in remission [
1]. A state of true remission [
2] is the main therapeutic objective of RA, and certainly MDA [
3] is becoming a more realistic goal owing to intensified treatment with disease-modifying anti-rheumatic drugs (DMARDs) [
4]. We showed treat-to-target regimens such as Combinatietherapie bij Reumatoïde Artritis (COBRA) or COBRA-light therapy—comprising methotrexate (MTX) with or without sulfasalazine (SSZ) and high-dose or moderate-dose prednisolone respectively—to be effective in establishing MDA or remission, at least partly by their target design in which patients without a favorable response (clinical remission) are offered other, probably more powerful, antirheumatic drugs [
5,
6]. In addition, once drug-induced remission has been achieved, prevention of structural damage is most likely if remission is maintained [
7]. Unfortunately, recurrent flares are common in RA patients [
8‐
10]. Furthermore, there is evidence that progression of joint damage may proceed despite the absence of clinical synovitis—that is, in patients with MDA or in remission—presumably due to the presence of subclinical disease activity [
11,
12]. In contrast to conventional X-ray scanning, advanced imaging techniques such as magnetic resonance imaging (MRI), ultrasound (US), and positron emission tomography (PET) allow detection and quantification of subclinical synovitis [
13‐
16]. MRI and US abnormalities are associated with future radiological damage and flaring in RA (remission) patients [
12,
15‐
20], but this association is not very strong [
21], leaving room for alternative imaging techniques that could further contribute to specificity.
PET depicts biological targets and can be used for sensitive detection of inflammation at molecular and cellular levels. Macrophage-targeting PET tracers, such as
11C-(
R)
-PK11195 (1-(2-chlorophenyl)-
N-methyl-
N-(1-methylpropyl)-3-isoquinoline carboxamide), can visualize inflammatory processes. We have recently shown that PET and macrophage targeting is a promising technique for identification of longstanding RA patients with signs of subclinical synovitis related to short-term flare [
15], but such studies have not yet been conducted in early RA patients.