Early prediction of treatment response in rheumatoid arthritis by quantitative macrophage PET

Abstract

ObjectiveTo determine whether macrophage positron emission tomography (PET)/computed tomography (CT) imaging using (R)-[11C]PK11195 at 0 and 2 weeks is associated with clinical response at 13 weeks in patients with early rheumatoid arthritis (RA).MethodsWhole-body (R)-[11C]PK11195 PET/CT scans were performed at baseline and after 2 weeks of COBRA-light (combination therapy of methotrexate and prednisone) treatment in 35 patients with clinically active early RA. Clinical assessment (Disease Activity Score of 44 joints (DAS44)) was performed at 0, 2 and 13 weeks of treatment. PET/CT scans were assessed visually by two blinded, experienced readers, and by calculating standardised uptake values (SUVs) for shoulders, elbows, hips, knees, and hand and feet joints. Clinical and PET variables were compared using (multivariate) linear regression.Results18 males and 17 females were included (baseline DAS44=3.2 ± 1.0). 171 out of 1470 joints were visually PET positive at baseline, decreasing to 100 joints after 2 weeks. In general, small feet joints showed the highest uptake at baseline, and the largest decrease after 2 weeks (Δ0-2). Neither baseline nor Δ0-2 PET measures correlated with DAS44 at 13 weeks. However, at 2 weeks, average SUV of the feet significantly correlated with DAS44 at 13 weeks (R2=0.14, p=0.04). In a multivariable model, DAS44 and average SUV of the feet at 2 weeks showed substantial combined predictive value (combined R2=0.297, p<0.01).ConclusionQuantitative macrophage PET assessment of feet joints, together with DAS44, after 2 weeks of COBRA light treatment in patients with early RA correlates with clinical response after 3 months of treatment.

Age, Sex, Metabolic and Pharmacologic Factors May Predict Nonresponse Status to Rheumatoid Arthritis Therapies

“…Primary non-response is attributed to therapy failure, whereas secondary non-response is associated with treatment failure caused by the immune milieu of each patient and its immunogenic response ability during repetitive inflammatory episodes. Non-response and antibody development are significant predictors of response to subsequent biological therapy, as indicated by certain studies (7)(8)(9)12). Providing precise definitions of primary and secondary non-response is crucial for predicting the most effective treatment for patients and enhancing clinical and practical guidance.…”

“…Early prediction of therapy response status for patients with RA continues to be a real challenge. Despite the recent development of several innovative diagnostic and therapeutic methods that combine clinical, radiological, and cellular (with special emphasis to immune cells) parameters, predictive assessment (8)(9)(10) of PNRS and SNRS remains a big problem for both patients and rheumatologists.…”

Metabolic and molecular imaging in inflammatory arthritis

“…51 52 Furthermore, Verweij et al were able to develop a multivariable predictive model of treatment response based on clinical data (DAS44) and whole-body 11 C-R-PK11195 PET/ CT scans which correlated with clinical response after 3 months of treatment. 53 To mitigate the issue of background uptake observed with 11 C-R-PK11195, a small number of exploratory studies on individuals with RA have introduced a further macrophage tracer binding to the β-folate receptor, 18 F-fluoro-PEG-folate (polyethylene glycol folate) which exploits the increased expression of folate receptors by activated macrophages. 41 54 Compared with 11 C-R-PK11195, it possesses substantial pharmacokinetic advantages, including rapid clearance and minimal background uptake, enabling a more accurate detection of inflammatory activity in all districts.…”

Challenges in Pharmacokinetic Modelling of [18F]fluoro-PEG-folate PET/CT Imaging in Epithelial Ovarian Cancer Patients

“…Many folate-based radiotracers have been studied for diagnostic and therapeutic purposes [7] with great preclinical results in FR-positive tumors [8]. The FR-targeting fluorine-18 labelled radiotracer [ 18 F]fluoro-polyethylene glycol(PEG)-folate [9] has shown promising results in the first in-human clinical studies evaluating its kinetic properties and performance in imaging of arthritic joints [10,11]. While in arthritis imaging the β-isoform of the folate receptor (FRβ) is targeted, in EOC patients the tumor specific imaging relies on targeting the α-isoform of the FR.…”