ABSTRACT
We aim to characterize the metabolic changes associated with early response to radiation therapy in a prostate cancer mouse model by 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) and [11C]acetate ([11C]ACT) positron emission tomography, with nuclear magnetic resonance (NMR) metabolomics corroboration. [18F]FDG and [11C]ACT PET were performed before and following irradiation (RT, 15Gy) for transgenic adenocarcinoma of mouse prostate xenografts. The underlying metabolomics alterations of tumor tissues were analyzed by using ex vivo NMR. The [18F]FDG total lesion glucose (TLG) of the tumor significant increased in the RT group at Days 1 and 3 post-irradiation, compared with the non-RT group (p < 0.05). The [11C]ACT maximum standard uptake value (SUVmax) in RT (0.83 ± 0.02) and non-RT groups (0.85 ± 0.07) were not significantly different (p > 0.05). The ex vivo NMR analysis showed a 1.70-fold increase in glucose and a 1.2-fold increase in acetate in the RT group at Day 3 post-irradiation (p < 0.05). Concordantly, the expressions of cytoplasmic acetyl-CoA synthetase in the irradiated tumors was overexpressed at Day 3 post-irradiation (p < 0.05). Therefore, TLG of [18F]FDG in vivo PET images can map early treatment response following irradiation and be a promising prognostic indicator in a longitudinal preclinical study. The underlying metabolic alterations was not reflected by the [11C]ACT PET.
Subject(s)
Acetates/chemistry , Carbon Radioisotopes/metabolism , Fluorodeoxyglucose F18/chemistry , Metabolomics , Positron-Emission Tomography , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/radiotherapy , Xenograft Model Antitumor Assays , Animals , Blotting, Western , Humans , Magnetic Resonance Spectroscopy , Male , Metabolome , Mice , Prostatic Neoplasms/pathology , Reproducibility of ResultsABSTRACT
PURPOSE: To assess the clinical value of proton (1 H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: 1 H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis. RESULTS: A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82. CONCLUSION: 1 H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:899-907.