We studied the feasibility of using the α-emitting ²¹³Bi-anti-CD20 therapy with direct bioluminescent tracking of micrometastatic human B-cell lymphoma in a SCID mouse model. Methods: A highly lethal SCID mouse model of minimal-tumor-burden disseminated non-Hodgkin lymphoma (NHL) was established using human Raji lymphoma cells transfected to express the luciferase reporter. In vitro and in vivo radioimmunotherapy experiments were conducted. Single- and multiple-dose regimens were explored, and results with ²¹³Bi-rituximab were compared with various controls, including no treatment, free ²¹³Bi radiometal, unlabeled rituximab, and ²¹³Bi-labeled anti-HER2/neu (non–CD20-specific antibody). ²¹³Bi-rituximab was also compared in vivo with the low-energy β-emitter ¹³¹I-tositumomab and the high-energy β-emitter ⁹⁰Y-rituximab. Results: In vitro studies showed dose-dependent target-specific killing of lymphoma cells with ²¹³Bi-rituximab. Multiple in vivo studies showed significant and specific tumor growth delays with ²¹³Bi-rituximab versus free ²¹³Bi, ²¹³Bi-labeled control antibody, or unlabeled rituximab. Redosing of ²¹³Bi-rituximab was more effective than single dosing. With a single dose of therapy given 4 d after intravenous tumor inoculation, disease in all untreated controls, and in all mice in the 925-kBq ⁹⁰Y-rituximab group, progressed. With 3,700 kBq of ²¹³Bi-rituximab, 75% of the mice survived and all but 1 survivor was cured. With 2,035 kBq of ¹³¹I-tositumomab, 75% of the mice were tumor-free by bioluminescent imaging and 62.5% survived. Conclusion: Cure of micrometastatic NHL is achieved in most animals treated 4 d after intravenous tumor inoculation using either ²¹³Bi-rituximab or ¹³¹I-tositumomab, in contrast to the lack of cures with unlabeled rituximab or ⁹⁰Y-rituximab or if there was a high tumor burden before radioimmunotherapy. α-emitter–labeled anti-CD20 antibodies are promising therapeutics for NHL, although a longer-lived α-emitter may be of greater efficacy.

^{我们研究了在 SCID 小鼠模型中使用 α 发射213 双}抗 CD20 疗法和直接生物发光追踪微转移性人 B 细胞淋巴瘤的可行性。方法：使用转染表达荧光素酶报告基因的人 Raji 淋巴瘤细胞，建立了一种高致死性 SCID 小鼠最小肿瘤负荷播散性非霍奇金淋巴瘤 (NHL) 模型。进行了体外和体内放射免疫治疗实验。探索了单剂量和多剂量方案，并将²¹³ Bi-rituximab 的结果与各种对照进行了比较，包括未治疗、游离²¹³ Bi 放射性金属、未标记的 rituximab 和²¹³ Bi 标记的抗 HER2/ neu（非 CD20 特异性抗体）。²¹³ Bi-rituximab 还在体内与低能 β-发射体¹³¹ I-tositumomab 和高能 β-发射体⁹⁰ Y-rituximab 进行了比较。结果：体外研究显示²¹³ Bi-rituximab 对淋巴瘤细胞的剂量依赖性靶标特异性杀伤。多项体内研究表明，与游离 213 Bi、213 Bi 标记的对照抗体或未标记的利妥昔单抗相比，213 双利妥昔单抗可显着且^特异性地^延缓肿瘤^生长。重做²¹³双利妥昔单抗比单次给药更有效。在静脉内肿瘤接种后 4 天给予单剂量治疗，所有未治疗的对照组和 925-kBq ⁹⁰ Y-利妥昔单抗组的所有小鼠的疾病都有进展。使用 3,700 kBq 的²¹³ Bi-rituximab，75% 的小鼠存活下来，除 1 只幸存者外，所有小鼠均得到治愈。使用 2,035 kBq 的¹³¹ I-tositumomab，通过生物发光成像，75% 的小鼠无肿瘤，62.5% 存活。结论：使用²¹³ Bi-rituximab 或¹³¹ I-tositumomab静脉注射肿瘤后 4 天治疗的大多数动物都实现了微转移性 NHL 的治愈，而未标记的 rituximab 或^{90无法治愈}Y-利妥昔单抗或放射免疫治疗前肿瘤负荷高。α-发射体标记的抗 CD20 抗体是很有前途的 NHL 治疗药物，尽管寿命更长的 α-发射体可能更有效。