Non-Hodgkin's lymphoma (NHL) is the fifth most common type of cancer in the United States, and diffuse large B cell lymphoma (DLBCL) is its most common subtype. Until recently DLCBL was rapidly and inevitably fatal, but the new standard of treatment with multi-drug immuno-chemotherapy combinations makes this form of cancer potentially curable in 40% of patients. The last hope for the majority for whom standard treatment will fail lies in more radical therapies such as bone marrow transplant. These alternate treatments are more risky, especially for patients already weakened by a failed attempt at standard immuno-chemotherapy. There is thus a great need for information that could allow oncologists to individualize treatment and immediately begin radical therapy in those for whom standard treatment is likely to fail. We believe our non-invasive measurement of NHL tumor metabolism with magnetic resonance spectroscopy (MRS) can provide this information. During previous periods of grant support, we have obtained promising initial results showing that the pre-treatment metabolic ratio of phosphoethanolamine (Etn-P) and phosphocholine (Cho-P), normalized by the tumor content of nucleotide triphosphates (NTP), can sensitively and specifically predict treatment failure in DLBCL.
The first aim for our multi-center study is to test our hypothesis that the [Etn-P + Cho-P]/NTP ratio is significantly correlated with treatment outcome in DLBCL. In addition to confirming our previous results with 31P MRS at the 1.5T field strength in an independent sample of patients, we also seek to extend these findings by studying the metabolism of DLBCL tumors with 31P at 3.0T, and also investigating absolute choline levels in DLBCL with 31P and 1H at both 1.5T and 3.0T.
Our second aim i s to follow up on initial indications that the significance of the correlation between the [Etn-P + Cho-P]/NTP ratio and treatment outcome is widely applicable to all forms of NHL and not merely the DLBCL subtype. We will approach this aim by accruing sufficient patients to analyze each subtype independently, using the 1.5T methods that are most directly applicable to the contemporary clinical environment. The proposed research is the final step leading a directed-therapy clinical trial and the culmination of an unprecedented program of translational research in MRS.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-P (O4))
Program Officer
Zhang, Huiming
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Schools of Medicine
New York
United States
Zip Code
Reyes-Vidal, Carlos M; Mojahed, Hamed; Shen, Wei et al. (2015) Adipose Tissue Redistribution and Ectopic Lipid Deposition in Active Acromegaly and Effects of Surgical Treatment. J Clin Endocrinol Metab 100:2946-55
Rata, Mihaela; Giles, Sharon L; deSouza, Nandita M et al. (2014) Comparison of three reference methods for the measurement of intracellular pH using 31P MRS in healthy volunteers and patients with lymphoma. NMR Biomed 27:158-62
Arias-Mendoza, Fernando; Payne, Geoffrey S; Zakian, Kristen et al. (2013) Noninvasive phosphorus magnetic resonance spectroscopic imaging predicts outcome to first-line chemotherapy in newly diagnosed patients with diffuse large B-cell lymphoma. Acad Radiol 20:1122-9
Lee, Seung-Cheol; Arias-Mendoza, Fernando; Poptani, Harish et al. (2012) Prediction and Early Detection of Response by NMR Spectroscopy and Imaging. PET Clin 7:119-26
Lee, Seung-Cheol; Poptani, Harish; Delikatny, E James et al. (2011) NMR metabolic and physiological markers of therapeutic response. Adv Exp Med Biol 701:129-35
Qi, Jing; Shukla-Dave, Amita; Fong, Yuman et al. (2011) 31P MR spectroscopic imaging detects regenerative changes in human liver stimulated by portal vein embolization. J Magn Reson Imaging 34:336-44
Sonabend, Adam M; Stuart, R Morgan; Yun, Jonathan et al. (2011) Prolonged intracerebral convection-enhanced delivery of topotecan with a subcutaneously implantable infusion pump. Neuro Oncol 13:886-93
Wijnen, J P; Scheenen, T W J; Klomp, D W J et al. (2010) 31P magnetic resonance spectroscopic imaging with polarisation transfer of phosphomono- and diesters at 3 T in the human brain: relation with age and spatial differences. NMR Biomed 23:968-76
Mellon, Eric A; Lee, Seung-Cheol; Pickup, Stephen et al. (2009) Detection of lactate with a hadamard slice selected, selective multiple quantum coherence, chemical shift imaging sequence (HDMD-SelMQC-CSI) on a clinical MRI scanner: Application to tumors and muscle ischemia. Magn Reson Med 62:1404-13
Klomp, D W J; Wijnen, J P; Scheenen, T W J et al. (2008) Efficient 1H to 31P polarization transfer on a clinical 3T MR system. Magn Reson Med 60:1298-305