Assessment of sensitivity, degradation and treatment response in two breast cancer xenograft models using HR MAS MRS

Abstract

Breast cancer is the most frequently form of cancer in women and new methods fordiagnostics and monitoring of treatment are desired. High resolution magic angle spin-ning magnetic resonance spectroscopy (HR MAS MRS) has shown to give a detailedmetabolic description of intact cancer tissue, which can be used to observed changes inmetabolism in different tumors.HR MAS MR spectra obtained from two breast cancer xenograft models characterizedas luminal-like and basal-like have been analyzed. Small samples of human breast cancerpatients are available, and beeing able to examine small samples is of great relevanceof MR metabolomics research.The results showed that small samples (5mg) allowed detection and quantificationof metabolites (creatine, choline, glyserophosphocholine, phosphocholine, glycine andglucose ). However, due to low signal to noise ratio (SNR) it was possible, thoughdifficult quantify the -glucose peak in the basal-like model. Therefore samples of size< 10mg or higher is preferable.This present study addresses problems in changes in metabolites level over time. HRMAS MR spectra from different time points of a spinning sample at 5 degrees over a timeperiod of 24 hours were obtained. Increased levels of glucose and increased glycine wasobserved in both tumor model. The basal-like model is also experiencing a decrease inglyserophosphocholine and increase in choline. Therefore keeping the experiment timebelow four hours is preferable.Principal component analysis (PCA) shows an increase in fatty acids due to treatmentof either doxorubucin or bevacizumab. This indicates that increase of fatty acids can beused as a biomarker for response of treatment in xenografts models. This can possiblealso be used for validation of treatment in human breast cancer patients.