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


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.
Molecular Imaging Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ming Q
MQ
Huang
David S
DS
Nelson
Stephen
S
Pickup
Hui
H
Qiao
E James
EJ
Delikatny
Harish
H
Poptani
Jerry D
JD
Glickson
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D054713:Bryostatins / Q000008:administration & dosage; D002794:Choline / Q000032:analysis; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005994:Glycerophosphates / Q000032:analysis; D006801:Humans; D006859:Hydrogen; D007773:Lactates / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009711:Nucleotides / Q000032:analysis; D010758:Phosphorus; D011241:Prednisone / Q000008:administration & dosage; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D054713:Bryostatins; D005994:Glycerophosphates; D007773:Lactates; D009711:Nucleotides; D010758:Phosphorus; C046785:bryostatin 1; D014750:Vincristine; D006859:Hydrogen; D004317:Doxorubicin; D003520:Cyclophosphamide; D002794:Choline; D011241:Prednisone