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 ofNMRmethods for prediction and early detection of response.Amulticenter study, in which we have participated, has already shown that pre-treatment³¹ 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 ³¹PMRS is limited to relatively large superficial tumors, we have been exploring ¹HMRS andMRI 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 ¹H 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.