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Abstract #4035

Quantitative 31P Magnetic Resonance Spectroscopy Stratifies Treatment Response to a PI3K/mTOR Inhibitor in Two Distinct Breast Cancer Xenografts

Morteza Esmaeili1, Tone Frost Bathen1, Olav Engebrthen2, 3, Gunhild Maelandsmo2, Ingrid Susann Gribbestad4, Siver A. Moestue1

1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 2Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 3Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospital, Oslo, Norway; 4Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway

The phosphatidylinositol-3-kinase (PI3K) signaling pathway promotes cell proliferation and survival of cancer cells. Inhibitors of this pathway are under investigation as targeted anticancer treatments. The aim of this study was to develop a phosphorus high resolution magic angle spinning (31P HR MAS) magnetic resonance spectroscopy (MRS) protocol for quantifying phosphorylated metabolites of importance in two distinct breast cancer xenografts, and to use this method for identifying biomarkers for response to PI3K inhibition. In basal-like xenografts, BEZ235 treatment induced a significant decrease in PE whilst PC and GPC were significantly increased. No significant metabolic changes were observed in luminal-like xenografts.

Keywords

acquisition activated activity allowing alpha alterations animal anticancer assigned background basal biology blotting blue breast calibrated calibration cancer cell cells chemical chemicals choline circulation clinical column comparing concentration conditions consistent containing control controls course daily days decoupling decrease decreases degradation depending described detected develop dissolved distinct dose drug drugs dual enzyme enzymes evaluated excitation explained expression faculty filtered findings fold free genetically glycerol hospital identical identifying improved in vivo include indicated individual induced inhibition inhibitor inhibitors institute intracellular inverse investigation involved like magic medical medicine metabolic metabolites models molecular monitoring pathway peak peaks phosphate phosphorus plus powerful previously principle probed profiling promising promotes proteins protocol pulse quantified quantifying quantitative received receiving reduction regulations reported representative representing resolution respect response revealed samples science significantly spec spectra spectral spectrometer spectroscopy spinning studies subtypes successfully suggest sweep targeted targeting technology therapy thereby tissue tissues tool transients translated treated treatment treatments triplet tumor type vehicle western whilst