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N‐acetyl resonances in in vivo and in vitro NMR spectroscopy of cystic ovarian tumors
Authors:Eva Kolwijck  Udo F. Engelke  Marinette van der Graaf  Arend Heerschap  Henk J. Blom  M'Hamed Hadfoune  Wim A. Buurman  Leon F. Massuger  Ron A. Wevers
Affiliation:1. Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;2. Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;3. Department of Obstetrics and Radiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;4. Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands;5. Department of Surgery, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Academic Hospital Maastricht and Maastricht University, Maastricht, The Netherlands
Abstract:An unassigned and prominent resonance in the region from δ 2.0–2.1 ppm has frequently been found in the in vivo MR spectra of cancer patients. We demonstrated the presence of this resonance with in vivo MRS in the cyst fluid of a patient with an ovarian tumor. 1H‐NMRS on the aspirated cyst fluid of this patient confirmed the observation. A complex of resonances was observed between 2.0 and 2.1 ppm. It was also present in 11 additional ovarian cyst fluid samples randomly chosen from our biobank. The resonance complex was significantly more prominent in samples from mucinous tumors than in samples from other histological subtypes. A macromolecule (>10 kDa) was found responsible for this complex of resonances. A correlation spectroscopy (COSY) experiment revealed cross peaks of two different types of bound sialic acid suggesting that N‐glycans from glycoproteins and/or glycolipids cause this resonance complex. In the literature, plasma α‐1 acid glycoprotein (AGP), known for its high content of N‐linked glycans, has been suggested to contribute to the δ 2.0–2.1 spectral region. The AGP cyst fluid concentration did not correlate significantly with the peak height of the δ 2.0–2.1 resonance complex in our study. AGP may be partly responsible for the resonance complex but other N‐acetylated glycoproteins and/or glycolipids also contribute. After deproteinization of the cyst fluid, N‐acetyl‐L ‐aspartic acid (NAA) was found to contribute significantly to the signal in this spectral region in three of the 12 samples. GC‐MS independently confirmed the presence of NAA in high concentration in the three samples, which all derived from benign serous tumors. We conclude that both NAA and N‐acetyl groups from glycoproteins and/or glycolipids may contribute to the δ 2.0–2.1 ppm resonance complex in ovarian cyst fluid. This spectral region seems to contain resonances from biomarkers that provide relevant clinical information on the type of ovarian tumor. Copyright © 2009 John Wiley & Sons, Ltd.
Keywords:α  1‐acid glycoprotein  biomarker  cyst fluid  1H‐NMR spectroscopy  magnetic resonance spectroscopy  N‐acetyl‐L‐aspartic acid  ovarian tumor
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