Title |
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
|
---|---|
Published in |
Arthritis Research & Therapy, November 2016
|
DOI | 10.1186/s13075-016-1166-z |
Pubmed ID | |
Authors |
Stefan Bruijnen, Michel Tsang-A-Sjoe, Hennie Raterman, Tamara Ramwadhdoebe, Daniëlle Vugts, Guus van Dongen, Marc Huisman, Otto Hoekstra, Paul-Peter Tak, Alexandre Voskuyl, Conny van der Laken |
Abstract |
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. 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. 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. 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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 57 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 11 | 19% |
Researcher | 10 | 18% |
Other | 6 | 11% |
Student > Bachelor | 3 | 5% |
Student > Master | 3 | 5% |
Other | 9 | 16% |
Unknown | 15 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 24 | 42% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 5% |
Chemistry | 3 | 5% |
Agricultural and Biological Sciences | 2 | 4% |
Immunology and Microbiology | 2 | 4% |
Other | 5 | 9% |
Unknown | 18 | 32% |