Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using 213 Bi-Anti-CD20 Monoclonal Antibody

The Journal of Nuclear Medicine

article

James Engles¹  Martin Brechbiel²  George Sgouros¹  Richard L. Wahl³  Gregory T. Havlena⁴  Nirav S. Kapadia⁵  Peng Huang¹  Hong Song⁶ 

[1] Johns Hopkins University School of Medicine;National Institutes of Health;Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine;Kaiser Permanente Radiology;Dartmouth–Hitchcock Medical Center;Section of Nuclear Medicine, Stanford University School of Medicine

关键词: 213Bi;    alpha emitter;    B-cell non-Hodgkin lymphoma;    animal model;    bioluminescence;    radioimmunotherapy;   

DOI  :  10.2967/jnumed.122.263962

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

CC BY