B-cell imaging with zirconium-89 labelled rituximab PET-CT at baseline is associated with therapeutic response 24 weeks after initiation of rituximab ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-11-18

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

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. More... »

PAGES

266

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13075-016-1166-z

DOI

http://dx.doi.org/10.1186/s13075-016-1166-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028761351

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27863504


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27 schema:description 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.
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34 schema:keywords B cells
35 B-cell counts
36 CD22
37 European League
38 LN tissue
39 League
40 Ln
41 MethodsWe
42 PET data
43 PET-CT
44 RA responders
45 Rheumatism (EULAR) response criteria
46 Sjögren's disease
47 addition
48 anti-B-cell therapy
49 arthritis
50 arthritis patients
51 association
52 autoimmune diseases
53 baseline
54 biodistribution
55 biopsy
56 cells
57 clinical need
58 clinical response
59 clinical value
60 count
61 criteria
62 data
63 disease
64 dose
65 emission tomography
66 erythematosus
67 hand joints
68 imaging
69 initiation
70 joint uptake
71 joints
72 key players
73 lupus erythematosus
74 lymph node biopsy
75 means
76 need
77 negative predictive value
78 node biopsy
79 objective
80 pathogenesis
81 patients
82 players
83 positron emission tomography
84 potential responders
85 predictive value
86 promise
87 ratio
88 responders
89 response
90 response criteria
91 rheumatoid arthritis
92 rheumatoid arthritis patients
93 rituximab
94 rituximab treatment
95 specificity
96 study
97 systemic lupus erythematosus
98 therapeutic dose
99 therapy
100 tissue
101 tomography
102 treatment
103 unmet clinical need
104 uptake
105 values
106 week 24
107 weeks
108 weeks of treatment
109 zirconium-89
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