Jauw Yvonne W S, Zijlstra Josée M, de Jong Daphne, Vugts Danielle J, Zweegman Sonja, Hoekstra Otto S, van Dongen Guus A M S, Huisman Marc C
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
PLoS One. 2017 Jan 6;12(1):e0169828. doi: 10.1371/journal.pone.0169828. eCollection 2017.
Treatment of patients with diffuse large B cell lymphoma (DLBCL) includes rituximab, an anti-CD20 monoclonal antibody (mAb). Insufficient tumor targeting might cause therapy failure. Tumor uptake of 89Zirconium (89Zr)-mAb is a potential imaging biomarker for tumor targeting, since it depends on target antigen expression and accessibility. The aim of this pilot study was to describe the performance of 89Zr-labeled-rituximab-PET to assess CD20 targeting in patients with relapsed/refractory DLBCL.
Six patients with biopsy-proven DLBCL were included. CD20 expression was assessed using immunohistochemistry (IHC). 74 MBq 89Zr-rituximab (10 mg) was administered after the therapeutic dose of rituximab. Immuno-PET scans on day 0, 3 and 6 post injection (D0, D3 and D6 respectively) were visually assessed and quantified for tumor uptake.
Tumor uptake of 89Zr-rituximab and CD20 expression were concordant in 5 patients: for one patient, both were negative, for the other four patients visible tumor uptake was concordant with CD20-positive biopsies. Intense tumor uptake of 89Zr-rituximab on PET (SUVpeak = 12.8) corresponded with uniformly positive CD20 expression on IHC in one patient. Moderate tumor uptake of 89Zr-rituximab (range SUVpeak = 3.2-5.4) corresponded with positive CD20 expression on IHC in three patients. In one patient tumor uptake of 89Zr-rituximab was observed (SUVpeak = 3.8), while the biopsy was CD20-negative.
This study suggests a positive correlation between tumor uptake of 89Zr-rituximab and CD20 expression in tumor biopsies, but further studies are needed to confirm this. This result supports the potential of 89Zr-rituximab-PET as an imaging biomarker for CD20 targeting. For clinical application of 89Zr-rituximab-PET to guide individualized treatment, further studies are required to assess whether tumor targeting is related to clinical benefit of rituximab treatment in individual patients.
弥漫性大B细胞淋巴瘤（DLBCL）患者的治疗包括使用抗CD20单克隆抗体（mAb）利妥昔单抗。肿瘤靶向不足可能导致治疗失败。89锆（89Zr）标记的单克隆抗体的肿瘤摄取是一种潜在的肿瘤靶向成像生物标志物，因为它取决于靶抗原的表达和可及性。这项初步研究的目的是描述89Zr标记的利妥昔单抗PET在评估复发/难治性DLBCL患者中CD20靶向性方面的表现。
纳入6例经活检证实为DLBCL的患者。使用免疫组织化学（IHC）评估CD20表达。在给予治疗剂量的利妥昔单抗后，注射74 MBq的89Zr-利妥昔单抗（10 mg）。在注射后第0、3和6天（分别为D0、D3和D6）进行免疫PET扫描，对肿瘤摄取进行视觉评估和定量。
5例患者中89Zr-利妥昔单抗的肿瘤摄取与CD20表达一致：1例患者两者均为阴性，另外4例患者可见的肿瘤摄取与CD20阳性活检一致。1例患者PET上89Zr-利妥昔单抗的强烈肿瘤摄取（SUV峰值 = 12.8）与IHC上CD20的均匀阳性表达相对应。3例患者中89Zr-利妥昔单抗的中度肿瘤摄取（SUV峰值范围 = 3.2 - 5.4）与IHC上CD20的阳性表达相对应。1例患者观察到89Zr-利妥昔单抗的肿瘤摄取（SUV峰值 = 3.8），而活检显示CD20阴性。
本研究表明89Zr-利妥昔单抗的肿瘤摄取与肿瘤活检中的CD20表达之间存在正相关，但需要进一步研究来证实这一点。这一结果支持了89Zr-利妥昔单抗PET作为CD20靶向成像生物标志物的潜力。对于89Zr-利妥昔单抗PET在指导个体化治疗中的临床应用，需要进一步研究来评估肿瘤靶向是否与个体患者利妥昔单抗治疗的临床获益相关。
