Abstract
BackgroundB cells are key players in the pathogenesis of rheumatoid arthritis (RA). Although successful in 50–60% of patients with RA, anti-B-cell therapy given as rituximab could be more efficient by identifying potential responders prior to treatment. Positron emission tomography (PET) using radiolabeled rituximab for B-cell imaging might provide the means to fulfil this unmet clinical need. The objective of this study was to investigate the association between biodistribution of zirconium-89 (89Zr)-rituximab on PET-computed tomography (CT) and clinical response in patients with RA.MethodsWe included 20 patients with RA who were starting rituximab treatment. At the first intravenous (i.v.) therapeutic dose, patients were also injected with 89Zr-rituximab, followed by PET-CT. European League Against Rheumatism (EULAR) response criteria were applied to determine response at week 24. PET-CT was analyzed visually and quantitatively. Lymph node (LN) biopsies were performed at 0 and 4 weeks to correlate B-cell counts with imaging data.ResultsPET-positive hand joints (range 1–20) were observed in 18/20 patients. Responders had significantly higher 89Zr-rituximab uptake in PET-positive hand joints than non-responders (median target-to-background (T/B)) ratios (IQR) were 6.2 (4.0–8.8) vs. 3.1 (2.2–3.9), p = 0.02). At T/B ≥4.0, positive and negative predictive values for clinical response were respectively 90% and 75%. Quantitative 89Zr-rituximab hand joint uptake on PET correlated inversely with CD22+ B-cell count in LN tissue at 4 weeks of treatment (r = 0.6, p = 0.05). In addition, the CD22+ B-cell count in LN correlated positively with quantitative LN PET data at baseline, supporting the specificity of B-cell imaging on PET.ConclusionsNon-invasive B-cell imaging by 89Zr-rituximab PET-CT has promising clinical value to select RA responders to rituximab at baseline. 89Zr-rituximab PET-CT may also hold promise for monitoring anti-B-cell therapies in other B-cell driven autoimmune diseases, such as systemic lupus erythematosus and Sjögren’s disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1166-z) contains supplementary material, which is available to authorized users.
Highlights
B cells are key players in the pathogenesis of rheumatoid arthritis (RA)
Targeted depletion of B cells with a monoclonal antibody such as rituximab appears to be efficient and cost-effective in patients with RA that is refractory to disease-modifying anti-rheumatic drugs (DMARDS) and anti-tumor necrosis factor-alpha therapy [1,2,3]
Clinical data Positron emission tomography (PET)-computed tomography (CT) scans were obtained in 20 patients and lymph node biopsies in 17 patients (Table 1)
Summary
Successful in 50–60% of patients with RA, anti-B-cell therapy given as rituximab could be more efficient by identifying potential responders prior to treatment. Positron emission tomography (PET) using radiolabeled rituximab for B-cell imaging might provide the means to fulfil this unmet clinical need. Apart from prediction of disease outcome in RA [7, 8], our group has previously demonstrated that PET predicts infliximab outcome as early as two weeks after initiation of treatment [9]. This predictive value for therapeutic outcome was later confirmed by Roivainen et al for early DMARD combination treatment [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
