Metabolic characterization of human non-Hodgkin's lymphomas in vivo with the use of proton-decoupled phosphorus magnetic resonance spectroscopy.
Development of biological and clinical uses of in vivo 31P magnetic resonance spectroscopy has been hampered by poor anatomic localization of spectra and poor resolution of overlapping signals within phosphomonoester and phosphodiester regions of the spectrum. We applied 1H-decoupling and nuclear Overhauser enhancement to improve resolution of 31P magnetic resonance spectra accurately localized to 21 non-Hodgkin's lymphomas (NHL) by using three-dimensional chemical shift imaging. All 21 spectra had large phosphomonoester signals (26% of total phosphorus) that contained high amounts of phosphoethanolamine relative to phosphocholine. There were no signals from glycerophosphoethanolamine or glycerophosphocholine but only a broad signal from membrane phospholipids in the phosphodiester region (20% of phosphorus). Prominent nucleoside triphosphates (47% of phosphorus) and low inorganic phosphate (7% of phosphorus) indicate well-perfused tissue with viable cells. Mean intracellular pH was 7.23. These characteristics were similar in all grades and stages of NHL. By analogy with recently reported studies in cell lines in vitro, we hypothesize that the pattern of phospholipid metabolites observed in NHL in vivo is partly a manifestation of sustained activation of phospholipase C or D. The techniques we implemented permitted us to obtain more information about in vivo metabolism of NHL than has heretofore been available. This information is important for the establishment of appropriate experimental models and provides a basis from which to examine potential clinical uses of 31P magnetic resonance spectroscopy.
Negendank
W G
WG
Department of Nuclear Magnetic Resonance and Medical Spectroscopy, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Padavic-Shaller
K A
KA
Li
C W
CW
Murphy-Boesch
J
J
Stoyanova
R
R
Krigel
R L
RL
Schilder
R J
RJ
Smith
M R
MR
Brown
T R
TR
D019794:2,3-Diphosphoglycerate; D000328:Adult; D000368:Aged; D011756:Diphosphates / Q000378:metabolism; D004163:Diphosphoglyceric Acids / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism
D011756:Diphosphates; D004163:Diphosphoglyceric Acids; D004952:Esters; D004983:Ethanolamines; D010714:Phosphatidylethanolamines; D010725:Phosphocreatine; D010767:Phosphorylcholine; C002449:glycerophosphoethanolamine; D019794:2,3-Diphosphoglycerate; C005448:phosphorylethanolamine