WE-C-ValB-04: Magnetic Resonance Spectroscopy Detects Metabolic Changes Upon Chemotherapy of Human Non-Hodgkin's Lymphoma Xenografts

A preliminary multi‐institutional study has recently demonstrated that ratios of the hosphomonoesters, phosphoethanolamine plus phosphocholine, to NTP of human non‐Hodgkin's lymphoma (NHL) easured by 31P MRS before initiation of therapy can identify about 2/3 of the patients who will not exhibit a complete local clinical response. These patients should be encouraged to undergo more aggressive alternative therapy, which entails some risk of mortality but also offers hope of response, remission or cure. However, the limited sensitivity of 31P MRS limits its application mostly to large, superficial tumors. We have, therefore, been developing much more sensitive 1H MRS and MRI methods to examine smaller tumors. Here we report studies of mouse xenografts of the most common form of human NHL and the only form that exhibits cures (in about 1/3 of the patients) — diffuse large B‐cell lymphoma (DLCL2). In vivo 1H MRS using a selective multiple quantum coherence pulse sequence (Sel‐MQC) detected decreases of lactate and total choline in DLCL2 tumors treated with three cycles of CHOP (cyclophospamide, doxorubicin, vincristine, prednisone) chemotherapy with Bryostatin added to suppress expression of the mdr1 gene. Single voxel localized spectroscopy (STEAM) detected decreases in choline and lactate/lipid that accompanied response. These changes correlated decreases in phosphomonesters detected by 31P MRS with tumor growth delay. In vivo data were correlated with data on tumor extracts. Our data suggest that 1H MRS may provide a very sensitive method for detecting early response of human NHL to chemotherapy; 1H MRI studies of response are in progress.