Non-Hodgkin's Lymphoma (NHL) provides an excellent model with which to probe variations in cancer metabolism in vivo using NMR and to examine potential clinical and research uses of 31P magnetic resonance spectroscopy (MRS). NHL occurs in 3 grades with distinctly different histologic, biologic and clinical features. It is now well established that 31P NMR spectra of human cancers in vivo typically have metabolic characteristics which differ from those of normal tissues including elevated phosphomonoesters (PME), elevated phosphodiesters (PDE) and diminished phosphocreatine (PCR). In several studies, including those of lymphomas, one or more of these characteristics have been shown to provide useful diagnostic discriminants or prognostic indices. This background makes it clear that it is time to address the question """"""""What is the clinical utility of NMR spectroscopy in oncology?"""""""". The study we propose is a prospective trial in a large number of patients with a type of cancer (NHL) especially well suited to address this question, with careful attention paid to patient selection, protocol management and statistical analysis. To achieve the aims of this study, we will first develop dual-tuned 1H, 31P surface coils appropriate to access the wide variety of anatomic locations of NHL's, along with proton decoupling of 31P to distinguish individual components of the phospholipid metabolites (e.g., phosphocholine and phosphoethanolamine), 3D chemical shift imaging to localize 31P NMR spectra to the lymphoma mass, and quantitation of metabolites. We will test the hypothesis that malignant behavior correlates with metabolic status in the clinical setting by determining how the 3 grades of NHL differ in their 31P NMR spectra in regard to phospholipid metabolites, energy metabolites, and pH. We will test the hypothesis that the 31P NMR spectrum of NHL contains prognostic information that can predict response to treatment or eventual clinical outcome by relating these events to metabolic features in the baseline spectrum and to changes that occur in the spectrum upon initiation of treatment. Results of this study will pave the way for large clinical trials of MRS in other cancers, and for a clinical trial in which 31P MRS could be used to intervene in the selection of treatment regimens in individual patients with NHL.
