This application is from the FCCC. The 31-phosphorus (31-P) nuclear magnetic resonance (NMR) spectroscopy (MRS) resonance of human cancers in vivo reveals metabolic characteristics which differ from those of normal tissues. These include elevations in PME, PDE, and of cellular pH, and dimininution of PCr. Published studies show that MRS- derived pH and MRI-derived T2 relaxation time predict response of soft tissue sarcomas to radiation and hyperthermia, and that changes in PME's predict response of several different human cancers to chemotherapy and radiation. The applicant proposes a prospective trial to test the hypotheses that in vivo 31-P MRS can predict sensitivity or resistance to treatment inpatients with types of cancers especially well suited to determine the clinical utility of MRS in cancer management, in particular non-Hodgkin's lymphomas and locally-advanced primary breast cancers. This will be done by correlating response rate and disease-free survival to metabolic features in the baseline spectrum and to changes in the spectrum occurring early following initiation of treatment. This application is the central one of 8 interactive R01 applications from institutions cooperating to study over 1500 patients with non-Hodgkin's lymphomas, locally-advanced breast cancers,sarcomas, and carcinomas of the head and neck. Attention will be paid to patient selection, protocol management, technical quality control and statistical analyses. The state-of-the-art techniques used will be uniform across the 8 institutions and will include: (1) The use of dual-tuned proton/phosphorus surface coils to interrogate various tumor anatomical locations. (2) Proton-decoupling of phosphorus spectra to distinguish individual components of phospholipid metabolites in the PME and PDE regions. (3) Image-guided 3-dimensional chemical shift imaging to accurately localize 13P NMR spectra to tumor masses, and (4) Molar quantitation of metabolite concentrations in the tumors. This application also proposes to establish standards for cooperative MRS trials in other diseases and clinical settings, and seeks to pave the way for clinical trials in which MRS could be used to intervene in the selection of treatment regimens in individual patients with cancer.
