Abstract
BackgroundThis study was conducted in order to elucidate metabolic differences between human rectal cancer biopsies and colorectal HT29, HCT116 and SW620 xenografts by using high-resolution magnetic angle spinning (MAS) magnetic resonance spectroscopy (MRS) and for determination of the most appropriate human rectal xenograft model for preclinical MR spectroscopy studies. A further aim was to investigate metabolic changes following irradiation of HT29 xenografts.MethodsHR MAS MRS of tissue samples from xenografts and rectal biopsies were obtained with a Bruker Avance DRX600 spectrometer and analyzed using principal component analysis (PCA) and partial least square (PLS) regression analysis.Results and conclusionHR MAS MRS enabled assignment of 27 metabolites. Score plots from PCA of spin-echo and single-pulse spectra revealed separate clusters of the different xenografts and rectal biopsies, reflecting underlying differences in metabolite composition. The loading profile indicated that clustering was mainly based on differences in relative amounts of lipids, lactate and choline-containing compounds, with HT29 exhibiting the metabolic profile most similar to human rectal cancers tissue. Due to high necrotic fractions in the HT29 xenografts, radiation-induced changes were not detected when comparing spectra from untreated and irradiated HT29 xenografts. However, PLS calibration relating spectral data to the necrotic fraction revealed a significant correlation, indicating that necrotic fraction can be assessed from the MR spectra.
Highlights
This study was conducted in order to elucidate metabolic differences between human rectal cancer biopsies and colorectal HT29, HCT116 and SW620 xenografts by using high-resolution magnetic angle spinning (MAS) magnetic resonance spectroscopy (MRS) and for determination of the most appropriate human rectal xenograft model for preclinical MR spectroscopy studies
We investigated the changes in biochemical composition of HT29 xenografts following 15 Gy irradiation
Spectral assignment Representative CPMG spin-echo high resolution (HR) MAS MR spectra of the colorectal xenografts SW620, HCT116 and HT29 are presented in Fig. 1 together with the spin-echo spectra from a human rectal adenocarcinoma biopsy
Summary
This study was conducted in order to elucidate metabolic differences between human rectal cancer biopsies and colorectal HT29, HCT116 and SW620 xenografts by using high-resolution magnetic angle spinning (MAS) magnetic resonance spectroscopy (MRS) and for determination of the most appropriate human rectal xenograft model for preclinical MR spectroscopy studies. With the use of new technology and the availability of transgenic animals, molecular mechanisms of several diseases can be explored. In order for an animal model to serve as a useful model for human disease, the modeled disease must be similar in etiology and function to the human equivalent. Characterization of tissue at the molecular level will elucidate differences and similarities between metabolic profiles of human rectal cancer and xenografts. Knowledge of the metabolic profile of a xenograft can be important for its predictive value as tumor model in preclinical biomedical research
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