Efficacy and MRI of rituximab and methotrexate treatment in a nude rat model of CNS lymphoma.
To determine the efficacy of methotrexate and/or rituximab in a CNS lymphoma model and to evaluate MRI modalities for monitoring efficacy, we inoculated female athymic nude rats (rnu/rnu) intracerebrally with human MC116 B-lymphoma cells. Between days 16 and 26, rats were randomized to receive intravenous (IV) treatment with (1) saline (controls, n = 15), (2) methotrexate 1,000 mg/m(2) (n = 6), (3) rituximab 375 mg/m(2) (n = 6), or (4) rituximab plus methotrexate (n = 6). T2/fluid-attenuated inversion recovery (FLAIR) and gadolinium contrast-enhanced T1 MRI sequences were performed prior to and 1 week after treatment. IV rituximab gave an objective tumor response in four of six animals (>50% reduction in tumor volume comparing pre- and posttreatment T2/FLAIR MRI) and resulted in stable disease (50%-125% of baseline) in another animal. The percent change in tumor volume on T2/FLAIR images was significantly different in the control versus rituximab group (p = 0.0051). IV methotrexate slowed tumor growth, compared to controls, but only one of six animals had an objective response. In untreated controls, tumor histological volumes correlated well with T2/FLAIR or contrast-enhanced T1 images (r = 0.877). In the treatment groups, T2/FLAIR correlation was good, but the gadolinium-enhanced T1 MRI was not significantly correlated with histology (r = 0.19). The MC116 CNS lymphoma model seems valuable for preclinical testing of efficacy and toxicity of treatment regimens. IV rituximab was highly effective, but methotrexate was only minimally effective. T2/FLAIR was superior to contrast-enhanced T1 for monitoring efficacy.
Jahnke
Kristoph
K
Department of Neurology, Neuro-Oncology, and Blood-Brain Barrier Program, Oregon Health and Science University, Portland, OR, USA.
Muldoon
Leslie L
LL
Varallyay
Csanad G
CG
Lewin
Seth J
SJ
Brown
Robert D
RD
Kraemer
Dale F
DF
Soussain
Carole
C
Neuwelt
Edward A
EA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007089:Image Enhancement; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008727:Methotrexate / Q000008:administration & dosage*; D051381:Rats; D011923:Rats, Nude; D000069283:Rituximab; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D008727:Methotrexate