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Purpose To study cancer associated with abnormal metabolism of phospholipids, of which several have been proposed as biomarkers for malignancy or to monitor response to anticancer therapy. We explored 3D 31P magnetic resonance spectroscopic imaging (MRSI) at high magnetic field for in vivo assessment of individual phospholipids in two patient-derived breast cancer xenografts representing good and poor prognosis (luminal- and basal-like tumors). Materials and Methods Metabolic profiles from luminal-like and basal-like xenograft tumors were obtained in vivo using 3D 31P MRSI at 11.7T and from tissue extracts in vitro at 14.1T. Gene expression analysis was performed in order to support metabolic differences between the two xenografts. Results In vivo 31P MR spectra were obtained in which the prominent resonances from phospholipid metabolites were detected at a high signal-to-noise ratio (SNR >7.5). Metabolic profiles obtained in vivo were in agreement with those obtained in vitro and could be used to discriminate between the two xenograft models, based on the levels of phosphocholine, phosphoethanolamine, glycerophosphocholine, and glycerophosphoethanolamine. The differences in phospholipid metabolite concentration could partly be explained by gene expression profiles. Conclusion Noninvasive metabolic profiling by 3D 31P MRSI can discriminate between subtypes of breast cancer based on different concentrations of choline- and ethanolamine-containing phospholipids. © 2014 Wiley Periodicals, Inc. This is the authors' manuscript to the article.

PURPOSE: Phospholipid metabolites are of importance in cancer studies, and have been suggested as candidate metabolic biomarkers for response to targeted anticancer drugs. The purpose of this study was to develop a phosphorus (31P) high resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) protocol for quantification of phosphorylated metabolites in intact cancer tissue. METHODS: 31P spectra were acquired on a 14.1 T spectrometer with a triplet 1H/13C/31P MAS probe. Quantification of metabolites was performed using the PULCON principle. Basal-like and luminal-like breast cancer xenografts were treated with the dual PI3K/mTOR inhibitor BEZ235, and the impact of treatment on the concentration of phosphocholine (PCho), glycerophosphocholine (GPC), phosphoethanolamine (PEtn) and glycerophosphoethanolamine (GPE) was evaluated. RESULTS: In basal-like xenografts, BEZ235 treatment induced a significant decrease in PEtn (-25.6%, P = 0.01) whilst PCho (16.5%, P = 0.02) and GPC (37.3%, P < 0.001) were significantly increased. The metabolic changes could partially be explained by increased levels of phospholipase A2 group 4A (PLA2G4A). CONCLUSION: 31P HR-MAS MRS is a useful method for quantitative assessment of metabolic responses to PI3K inhibition. Using the PULCON principle for quantification, the levels of PCho, GPC, PEtn and GPE could be evaluated with high precision and accuracy. © 2013 Wiley Periodicals, Inc. This is the peer reviewed version of the article, which has been published in final form at dx.doi.org/10.1002/mrm.24869. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.