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

摘要

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 immuno deficient 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 to tal choline (tCho) were detected using the selective multiple quantum coherence sequence and the stimulated e cho 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/H_ r2atio hOad decreased significantly (5%, P = 0.003), whereas the Lac/H_r0a2=a.5t ni8o) dh. Ba dot tnhCoO Lth ach/oaHn/ged (P H_0h02=P.a0.d10 d60e, cr1eresap;Os e1cdti0 vaef%tlye)r. ,o Anfete cry tcwleo cfy RclCeHsOP treatment (26%, 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/H_2O are more sensitive indices of response to rituximab, whereas decreases in Lac/H_ 2O are more sensitive to response to CHOP combination therapy.