title: NMR metabolic and physiological markers of therapeutic response.
abstract: Identification of reliable metabolic and physiological NMR detectable markers for prediction and early detection of therapeutic response is essential to enabling NMR guided individualized therapy for cancer. Because non-Hodgkin's lymphoma (NHL) is a prevalent form of cancer that exhibits~50% response to therapy and often presents with large superficial lesions easily accessible to multinuclear magnetic resonance spectroscopy (MRS) measurements, it is an ideal test bed for development of NMR methods for prediction and early detection of response.A multicenter study, in which we have participated, has already shown that pre-treatment(31) PMRS measurement of the phosphate monoester (PME)to nucleoside triphosphate (NTP) ratio can identify about 2/3 of the patients who are destined not to exhibit a complete clinical response to a variety of therapeutic agents.Because (31)PMRS is limited to relatively large superficial tumors, we have been exploring (1)HMRS and MRI methods for early detection of therapeutic response. Using xenografts of the most common form of human NHL, diffuse large B-cell lymphoma (DLBCL), we have detected therapeutic response within one cycle of therapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), rituximab plus CHOP (RCHOP) or radiation (15 Gy) through detection of a decrease in lactic acid (Lac) or total choline (tCho) and an increase of apparent diffusion coefficients (ADC). We have also performed (1)H MRS of NHL patients in a clinical scanner. One of the patients exhibited a 70% decrease in Lac within 48 h of treatment with RCHOP.
authors: Laboratory of Molecular Imaging, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. seungch@mail.med.upenn.edu
authors: Seung-Cheol
authors: SC
authors: Lee
authors: Harish
authors: H
authors: Poptani
authors: E James
authors: EJ
authors: Delikatny
authors: Stephen
authors: S
authors: Pickup
authors: David S
authors: DS
authors: Nelson
authors: Stephen J
authors: SJ
authors: Schuster
authors: Sunita D
authors: SD
authors: Nasta
authors: Jakub
authors: J
authors: Svoboda
authors: Steven C
authors: SC
authors: Goldstein
authors: Stephen G
authors: SG
authors: Wallace
authors: Laurie A
authors: LA
authors: Loevner
authors: Eric A
authors: EA
authors: Mellon
authors: Ravinder
authors: R
authors: Reddy
authors: Jerry D
authors: JD
authors: Glickson
mesh_terms: D000368:Aged; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D011241:Prednisone / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D019344:Lactic Acid; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002794:Choline; D011241:Prednisone