Esmaeili Morteza, Bathen Tone F, Engebråten Olav, Mælandsmo Gunhild M, Gribbestad Ingrid S, Moestue Siver A
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Magn Reson Med. 2014 Jun;71(6):1973-81. doi: 10.1002/mrm.24869. Epub 2013 Jul 22.
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 ((31) P) high resolution magic angle spinning magnetic resonance spectroscopy protocol for quantification of phosphorylated metabolites in intact cancer tissue.
(31) P spectra were acquired on a 14.1 T spectrometer with a triplet (1) H/(13) C/(31) P 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, glycerophosphocholine, phosphoethanolamine and glycerophosphoethanolamine was evaluated.
In basal-like xenografts, BEZ235 treatment induced a significant decrease in phosphoethanolamine (-25.6%, P = 0.01) whilst phosphocholine (16.5%, P = 0.02) and glycerophosphocholine (37.3%, P < 0.001) were significantly increased. The metabolic changes could partially be explained by increased levels of phospholipase A2 group 4A (PLA2G4A).
(31) P high resolution magic angle spinning magnetic resonance spectroscopy is a useful method for quantitative assessment of metabolic responses to PI3K inhibition. Using the PULCON principle for quantification, the levels of phosphocholine, glycerophosphocholine, phosphoethanolamine, and glycerophosphoethanolamine could be evaluated with high precision and accuracy.
磷脂代谢产物在癌症研究中具有重要意义，并且已被认为是针对靶向抗癌药物反应的候选代谢生物标志物。本研究的目的是开发一种用于完整癌症组织中磷酸化代谢产物定量的磷（³¹P）高分辨率魔角旋转磁共振波谱方案。
在配备三重共振（¹H/¹³C/³¹P）魔角旋转探头的14.1 T光谱仪上采集³¹P谱。使用PULCON原理进行代谢产物的定量。用双重PI3K/mTOR抑制剂BEZ235处理基底样和腔面样乳腺癌异种移植瘤，并评估治疗对磷酸胆碱、甘油磷酸胆碱、磷酸乙醇胺和甘油磷酸乙醇胺浓度的影响。
在基底样异种移植瘤中，BEZ235治疗导致磷酸乙醇胺显著降低（-25.6%，P = 0.01），而磷酸胆碱（16.5%，P = 0.02）和甘油磷酸胆碱（37.3%，P < 0.001）显著增加。代谢变化部分可由磷脂酶A2第4A组（PLA2G4A）水平升高来解释。
³¹P高分辨率魔角旋转磁共振波谱是定量评估对PI3K抑制的代谢反应的有用方法。使用PULCON原理进行定量，可以高精度和准确性评估磷酸胆碱、甘油磷酸胆碱、磷酸乙醇胺和甘油磷酸乙醇胺的水平。
