Positron emission tomography with macrophage targeting to select individuals at risk for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a destructive disease if not treated timely and
effectively. Early and intensive treatment can limit joint damage and loss of
function. The ultimate aim of early intervention is prevention of clinically
active disease. A window of opportunity for very early intervention is the
pre-clinical phase. To acquire rules for early treatment in this phase, risk
stratification is needed. The presence of anti-citrullinated antibodies (ACPA
seropositivity) in the blood and painful joints (arthralgia) are risk factors
for development of clinical disease, and a prediction rule (including ACPA and
arthralgia characteristics) has been developed for further risk stratification.
However, a substantial portion (50-70%) of seropositive arthralgia patients
did not develop RA during this time frame. For such patients treatment with
associated side-effects may not be justified (at that time). Together with RA
patients that participated in organised project workshops, we agreed that it is
clinically acceptable for future arthralgia patients to participate in
intervention studies if a test had determined their one year risk to develop
arthritis to be equal or more than 80%. Therefore, additional predictive tests
are needed. Positron emission tomography (PET) and macrophage targeting might
be an innovative imaging technique with promising predictive value for
development of RA by non-invasive molecular imaging of the first signs of joint
inflammation (arthritis). The novel characteristics of PET of specific imaging
and quantification of binding sites of interest at molecular level in synovial
tissue distinguishes this technique from anatomical and functional techniques
as MRI and ultrasound. Our research group developed and investigated imaging of
arthritis by macrophage targeting and PET in various studies in RA patients.
More recently, we showed in a pilot study, that with tracer [11C]-(R)-PK11195
it is feasible to visualize arthritis activity before it becomes clinically
manifest (positive predictive value of 100%). Because the imaging
characteristics of the applied macrophage tracer were suboptimal to image more
subtle arthritis (sensitivity of 45%), we developed a novel macrophage tracer
called [18F]PEG-Folate with an improved arthritis imaging profile. A proof of
concept study and dynamic study have demonstrated the potential of this tracer
for the imaging of (sub)clinical arthritis.

This study has been transitioned to CTIS with ID 2024-513538-40-02 check the CTIS register for the current data.

To determine the value of quantitative whole body PET with [18F]PEG-Folate to
predict development of clinical arthritis within one year follow-up in
arthralgia patients with a positive autoantibody ACPA test.

A longitudinal, multicenter cohort PET study in 60 patients with arthralgia and
an increased risk to develop RA.

The study will involve a baseline whole body macrophage PET-CT scan follow by a
clinical follow-up period of one year to assess development of clinical
arthritis at 3, 6, 9 and 12 months.

The total radiation burden will be about 6.4 mSv.