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.
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 (89Zr)-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 with89Zr-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 higher89Zr-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%. Quantitative89Zr-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 by89Zr-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.
authors.affiliation: Amsterdam Rheumatology and immunology Center (ARC), location VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Stefan
authors.identifier: 0000-0003-2155-4929
authors.initials: S
authors.lastname: Bruijnen
authors.affiliation: Amsterdam Rheumatology and immunology Center (ARC), location VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Michel
authors.initials: M
authors.lastname: Tsang-A-Sjoe
authors.affiliation: Amsterdam Rheumatology and immunology Center (ARC), location VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hennie
authors.initials: H
authors.lastname: Raterman
authors.affiliation: Amsterdam Rheumatology and immunology Center (ARC), location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tamara
authors.initials: T
authors.lastname: Ramwadhdoebe
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Vugts
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Guus
authors.initials: G
authors.lastname: van Dongen
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Huisman
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Hoekstra
authors.affiliation: Amsterdam Rheumatology and immunology Center (ARC), location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Paul-Peter
authors.initials: PP
authors.lastname: Tak
authors.affiliation: Amsterdam Rheumatology and immunology Center (ARC), location VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Voskuyl
authors.affiliation: Amsterdam Rheumatology and immunology Center (ARC), location VU University Medical Center, Amsterdam, The Netherlands. J.vanderLaken@vumc.nl.
authors.forename: Conny
authors.initials: C
authors.lastname: van der Laken
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D001402:B-Lymphocytes / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011868:Radioisotopes / Q000493:pharmacokinetics; D000069283:Rituximab / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D015040:Zirconium / Q000493:pharmacokinetics
chemical_list: D018501:Antirheumatic Agents; D011868:Radioisotopes; D000069283:Rituximab; D015040:Zirconium
keywords: Clinical response; Positron-emission tomography; Rheumatoid arthritis; Rituximab; Treatment monitoring