In Vivo Monitoring Response to Chemotherapy of Human Diffuse Large B-Cell Lymphoma Xenografts in SCID Mice by 1H and 31P MRS

Abstract

Rationale and Objectives-A reliable non-invasive method for in vivo detection of early therapeutic response of non-Hodgkin's lymphoma (NHL) patients would be of great clinical value. This study evaluates the feasibility of 1 H and 31 P magnetic resonance spectroscopy (MRS) for in vivo detection of response to combination chemotherapy of human diffuse large B-cell lymphoma (DLCL2) xenografts in SCID mice.Materials and Methods. C-ombination chemotherapy with Cyclophosphamide, Hydroxydoxorubicin, Oncovin, Prednisone, and Bryostatin 1 (CHOPB) was administered to tumorbearing SCID mice weekly for up to four cycles. Spectroscopic studies were performed before the initiation of treatment and after each cycle of the CHOPB. Proton MRS for detection of lactate and total choline was performed using a selective multiple-quantum-coherence-transfer (Sel-MQC) and a spin-echo-enhanced Sel-MQC (SEE-Sel-MQC) pulse sequence, respectively. Phosphorus-31 MRS utilizing a non-localized single-pulse sequence without proton decoupling was performed on these animals.Results-Significant decreases in lactate and total choline were detected in the DLCL2 tumors after one cycle of CHOPB chemotherapy. The ratio of phosphomonoesters to β-nucleoside triphosphate (PME/βNTP, measured by 31 P MRS) significantly decreased in the CHOPB treated tumors after two cycles of CHOPB. The control tumors did not exhibit any significant changes in either of these metabolites.Conclusions-This study demonstrates that 1 H MRS and 31 P MRS can detect in vivo therapeutic response of NHL tumors and that lactate and choline offer a number of advantages over PMEs as markers of early therapeutic response.

Comparative Mitochondrial Proteomic Analysis of Raji Cells Exposed to Adriamycin

“…Although the mitochondrial proteins and their functional processes have been widely studied (9)(10)(11), little is known about mitochondrial proteome alterations of various cells or fractions after exposure to various conditions. Furthermore, although the effects of ADR on NHL have been investigated (12,13), most studies have focused only on evaluating single-protein changes and none on the total cellular proteome or the mitochondrial proteome. We selected Raji cells for study because Raji cells can serve as a model for human lymphomas with mutant p53 and increased BCL2 expression, which are commonly present in patients with NHL and are considered a source of chemotherapy failure in patients whose disease is chemoresistant (14).…”

Reproducibility of total choline/water ratios in mouse U87MG xenograft tumors by 1H‐MRS

“…Future studies are needed to assess the reproducibility of total cholineto-water ratios in xenografts of other tumor cell lines that may exhibit more necrosis and/or other tissue heterogeneities than U87MG tumors in the linear growth phase. Further, although the longest interval between scans was just 7 days in the present study, previous studies have indicated that 7 days is a sufficiently long interval to observe changes in metabolite ratios in xenografts produced by interventions including radiation (37) and oncolytic drugs (eg, [38][39][40].…”

High-field small animal magnetic resonance oncology studies

“…5, (Street et al , 1997; Darpolor et al , 2011a; Koutcher et al , 2000), and without 1 H decoupling and significant NOE enhancement (Fig. 6, (Huang et al , 2007)).…”