In vivo monitoring response to chemotherapy of human diffuse large B-cell lymphoma xenografts in SCID mice by 1H and 31P MRS

Acad Radiol. 2007 Dec;14(12):1531-9. doi: 10.1016/j.acra.2007.07.012.


Rationale and objectives: A reliable noninvasive 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 severe combined immunodeficient (SCID) mice.

Materials and methods: Combination chemotherapy with cyclophosphamide, hydroxy doxorubicin, Oncovin, prednisone, and bryostatin 1 (CHOPB) was administered to tumor-bearing 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 using a nonlocalized, single-pulse sequence without proton decoupling was also 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 beta-nucleoside triphosphate (PME/betaNTP, 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 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bryostatins / administration & dosage
  • Choline / analysis
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Feasibility Studies
  • Glycerophosphates / analysis
  • Humans
  • Hydrogen
  • Lactates / analysis
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Magnetic Resonance Spectroscopy / methods*
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation*
  • Nucleotides / analysis
  • Phosphorus
  • Prednisone / administration & dosage
  • Transplantation, Heterologous*
  • Treatment Outcome
  • Vincristine / administration & dosage


  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Bryostatins
  • Glycerophosphates
  • Lactates
  • Nucleotides
  • Phosphorus
  • bryostatin 1
  • Vincristine
  • Hydrogen
  • Doxorubicin
  • Cyclophosphamide
  • Choline
  • Prednisone

Supplementary concepts

  • CHOP protocol