Bruijnen Stefan, Tsang-A-Sjoe Michel, Raterman Hennie, Ramwadhdoebe Tamara, Vugts Daniëlle, van Dongen Guus, Huisman Marc, Hoekstra Otto, Tak Paul-Peter, Voskuyl Alexandre, van der Laken Conny
Amsterdam Rheumatology and immunology Center (ARC), location VU University Medical Center, Amsterdam, The Netherlands.
Amsterdam Rheumatology and immunology Center (ARC), location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Arthritis Res Ther. 2016 Nov 18;18(1):266. doi: 10.1186/s13075-016-1166-z.
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 (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 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 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 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 Zr-rituximab PET-CT has promising clinical value to select RA responders to rituximab at baseline. 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.
B细胞是类风湿关节炎（RA）发病机制中的关键因素。尽管利妥昔单抗治疗对50%-60%的RA患者有效，但在治疗前识别潜在的反应者可能会使抗B细胞治疗更有效。使用放射性标记的利妥昔单抗进行正电子发射断层扫描（PET）以进行B细胞成像，可能提供满足这一未满足临床需求的方法。本研究的目的是探讨89锆（Zr）-利妥昔单抗在PET计算机断层扫描（CT）上的生物分布与RA患者临床反应之间的关联。
我们纳入了20例开始接受利妥昔单抗治疗的RA患者。在首次静脉注射治疗剂量时，患者还注射了Zr-利妥昔单抗，随后进行PET-CT检查。应用欧洲抗风湿病联盟（EULAR）反应标准来确定第24周时的反应情况。对PET-CT进行了视觉和定量分析。在第0周和第4周进行淋巴结活检，以将B细胞计数与成像数据相关联。
20例患者中有18例观察到PET阳性的手部关节（范围为1-20个）。反应者在PET阳性手部关节中Zr-利妥昔单抗的摄取显著高于无反应者（中位靶本比（T/B）（四分位间距）分别为6.2（4.0-8.8）和3.1（2.2-3.9），p = 0.02）。当T/B≥4.0时，临床反应的阳性和阴性预测值分别为90%和75%。治疗4周时，PET上Zr-利妥昔单抗手部关节摄取量与淋巴结组织中CD22 B细胞计数呈负相关（r = 0.6，p = 0.05）。此外，基线时淋巴结中CD22 B细胞计数与定量淋巴结PET数据呈正相关，支持PET上B细胞成像的特异性。
Zr-利妥昔单抗PET-CT的非侵入性B细胞成像在基线时选择对利妥昔单抗有反应的RA患者方面具有有前景的临床价值。Zr-利妥昔单抗PET-CT在监测其他B细胞驱动的自身免疫性疾病（如系统性红斑狼疮和干燥综合征）的抗B细胞治疗方面也可能具有前景。
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