In vivo (1)H MRS of WSU-DLCL2 human non-Hodgkin's lymphoma xenografts: response to rituximab and rituximab plus CHOP.

Abstract

In order to identify early (1)H 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 approximately 600 mm(3), 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 ( approximately 5 days), whereas treatment with rituximab plus CHOP (RCHOP) led to approximately 20% tumor regression after three cycles of therapy. After one cycle of rituximab, the tCho/H(2)O ratio had decreased significantly (5%, P = 0.003), whereas the Lac/H(2)O ratio had not changed (P = 0.58). Both Lac/H(2)O and tCho/H(2)O 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 approximately 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/H(2)O are more sensitive indices of response to rituximab, whereas decreases in Lac/H(2)O are more sensitive to response to CHOP combination therapy.