B-cell imaging with zirconium-89 labelled rituximab PET-CT at baseline is associated with therapeutic response 24 weeks after initiation of rituximab treatment in rheumatoid arthritis patients

BACKGROUND: B 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 ((89)Zr)-rituximab on PET-computed tomography (CT) and clinical response in patients with RA.

METHODS: We included 20 patients with RA who were starting rituximab treatment. At the first intravenous (i.v.) therapeutic dose, patients were also injected with (89)Zr-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.

RESULTS: PET-positive hand joints (range 1-20) were observed in 18/20 patients. Responders had significantly higher (89)Zr-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 (89)Zr-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.

CONCLUSIONS: Non-invasive B-cell imaging by (89)Zr-rituximab PET-CT has promising clinical value to select RA responders to rituximab at baseline. (89)Zr-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.