Imaging and therapy with rituximab anti-CD20 immunotherapy in an animal model of central nervous system lymphoma

Leslie Muldoon, Seth J. Lewin, Edit Dósa, Dale Kraemer, Michael A. Pagel, Nancy Doolittle, Edward Neuwelt

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Abstract

Purpose: 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). Experimental Design: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)2207-2215
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number8
DOIs
StatePublished - Apr 15 2011

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Immunotherapy
Blood-Brain Barrier
Lymphoma
Central Nervous System
Animal Models
Methotrexate
Tumor Burden
Survival
Therapeutics
Monoclonal Antibodies
Nude Rats
Yttrium
Rituximab
B-Cell Lymphoma
Heterografts
Neoplasms
Research Design
Brain
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Imaging and therapy with rituximab anti-CD20 immunotherapy in an animal model of central nervous system lymphoma. / Muldoon, Leslie; Lewin, Seth J.; Dósa, Edit; Kraemer, Dale; Pagel, Michael A.; Doolittle, Nancy; Neuwelt, Edward.

In: Clinical Cancer Research, Vol. 17, No. 8, 15.04.2011, p. 2207-2215.

Research output: Contribution to journalArticle

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