In vivo1H MRS of WSU-DLCL2 human non-Hodgkin's lymphoma xenografts: response to rituximab and rituximab plus CHOP
Article first published online: 28 NOV 2008
Copyright © 2008 John Wiley & Sons, Ltd.
NMR in Biomedicine
Volume 22, Issue 3, pages 259–265, April 2009
How to Cite
Lee, S.-C., Delikatny, E. J., Poptani, H., Pickup, S. and Glickson, J. D. (2009), In vivo1H MRS of WSU-DLCL2 human non-Hodgkin's lymphoma xenografts: response to rituximab and rituximab plus CHOP. NMR Biomed., 22: 259–265. doi: 10.1002/nbm.1316
- Issue published online: 3 MAR 2009
- Article first published online: 28 NOV 2008
- Manuscript Accepted: 8 JUL 2008
- Manuscript Revised: 3 JUL 2008
- Manuscript Received: 22 APR 2008
- NIH. Grant Number: R01-CA101700-01A
- non-Hodgkin's lymphoma;
In order to identify early 1H MRS metabolic markers of response to rituximab immunotherapy and to rituximab plus CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, and prednisone) combination therapy, we performed an in vivo MRS investigation of a non-Hodgkin's lymphoma (NHL) xenograft model. Human WSU-DLCL2 NHL cells were subcutaneously implanted into flanks of female severe combined immunodeficient mice. When tumor volumes reached ∼600 mm3, rituximab was administered for three weekly cycles at a dose of 25 mg/kg per cycle with or without CHOP. Before and after treatment, tumor lactate (Lac) and total choline (tCho) were detected using the selective multiple quantum coherence sequence and the stimulated echo acquisition mode sequence, respectively. Rituximab produced a small tumor growth delay (∼5 days), whereas treatment with rituximab plus CHOP (RCHOP) led to ∼20% tumor regression after three cycles of therapy. After one cycle of rituximab, the tCho/H2O ratio had decreased significantly (5%, P = 0.003), whereas the Lac/H2O ratio had not changed (P = 0.58). Both Lac/H2O and tCho/H2O had decreased after one cycle of RCHOP treatment (26%, P = 0.001; 10%, P = 0.016, respectively). After two cycles of RCHOP, Ki67 assay of histological tumor specimens indicated ∼40% decrease in proliferation (P < 0.001) in the RCHOP-treated tumors; no change was detected after treatment with rituximab alone. This study suggests that decreases in tCho/H2O are more sensitive indices of response to rituximab, whereas decreases in Lac/H2O are more sensitive to response to CHOP combination therapy. Copyright © 2008 John Wiley & Sons, Ltd.