Department of Neurology, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
Clin Cancer Res. 2011 Apr 15;17(8):2207-15. doi: 10.1158/1078-0432.CCR-10-2923. Epub 2011 Mar 8.
To evaluate the effect of rituximab monoclonal antibody (mAb) on MRI tumor volumetrics and efficacy in a rat model of central nervous system (CNS) lymphoma when delivery to the brain was optimized with osmotic blood-brain barrier disruption (BBBD).
Female nude rats with intracerebral MC116 human B-cell lymphoma xenografts underwent baseline MRI and were randomized into 5 groups (n = 6 per group): (i) BBBD saline control; (ii) methotrexate with BBBD; (iii) rituximab with BBBD; (iv) rituximab and methotrexate with BBBD; and (v) intravenous rituximab. Tumor volumes were assessed by MRI at 1 week, and rats were followed for survival.
BBBD increased delivery of yttrium-90-radiolabeled mAb in the model of CNS lymphoma. Control rats showed 201 ± 102% increase in tumor volume on MRI 1 week after entering the study and median 14-day survival (range: 6-33). Tumor growth on MRI was slowed in the methotrexate treatment group, but survival time (median: 7 days; range: 5-12) was not different from controls. Among 17 evaluable rats treated with rituximab, 10 showed decreased tumor volume on MRI. All rituximab groups had increased survival compared with control, with a combined median of 43 days (range: 20-60, P < 0.001). There were no differences by route of delivery or combination with methotrexate.
Rituximab was effective at decreasing tumor volume and improving survival in a model of CNS lymphoma and was not affected by combination with methotrexate or by BBBD. We suggest that rituximab warrants further study in human primary CNS lymphoma.
评估利妥昔单抗单克隆抗体（mAb）在优化血脑屏障渗透性破坏（BBBD）以向大脑输送时对中枢神经系统（CNS）淋巴瘤大鼠模型的 MRI 肿瘤体积和疗效的影响。
患有颅内 MC116 人 B 细胞淋巴瘤异种移植物的雌性裸鼠进行基线 MRI 检查，并随机分为 5 组（每组 6 只）：（i）BBBD 盐水对照；（ii）甲氨蝶呤加 BBBD；（iii）利妥昔单抗加 BBBD；（iv）利妥昔单抗和甲氨蝶呤加 BBBD；和（v）静脉注射利妥昔单抗。在研究开始后 1 周通过 MRI 评估肿瘤体积，然后对大鼠进行生存随访。
BBBD 增加了 CNS 淋巴瘤模型中钇-90 放射性标记 mAb 的输送。对照组大鼠在进入研究后 1 周的 MRI 上显示肿瘤体积增加 201 ± 102%，中位 14 天存活期（范围：6-33）。甲氨蝶呤治疗组的肿瘤生长速度减慢，但存活时间（中位数：7 天；范围：5-12）与对照组无差异。在接受利妥昔单抗治疗的 17 只可评估大鼠中，10 只显示 MRI 上肿瘤体积减小。与对照组相比，所有利妥昔单抗组的生存时间均延长，中位生存时间为 43 天（范围：20-60，P < 0.001）。给药途径或与甲氨蝶呤联合使用没有差异。
利妥昔单抗在 CNS 淋巴瘤模型中可有效减小肿瘤体积并提高生存率，且不受与甲氨蝶呤联合或 BBBD 的影响。我们建议利妥昔单抗在原发性 CNS 淋巴瘤患者中进一步研究。
