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.
Highlights
Radiation therapy is widely used in the primary treatment for cancer, either alone or as a part of adjuvant or combination therapy [1,2]
The Response Evaluation Criteria in Solid Tumor (RECIST) criteria suggests that the time to evaluate treatment response of solid tumors is 6–8 weeks following treatment [17]
The aim of this study was to characterize the metabolic changes associated with early response to radiation therapy in a prostate cancer mouse model by using dual-tracer [18 F]FDG and [11 C]ACT PET, with in vitro cells and ex vivo tissue nuclear magnetic resonance (NMR) metabolomics corroboration
Summary
Radiation therapy is widely used in the primary treatment for cancer, either alone or as a part of adjuvant or combination therapy [1,2]. Accurate spatial localization is critical for optimal planning [3], and monitoring early radiation response can improve treatment efficacy and prognostic. Ionized radiations induce serial cellular and tissue responses, such as reactive oxygen species system [7,8], nuclear DNA damage [9], inflammation [10], apoptosis [11] and necrosis [12,13]. All of the biological alternations potentially serve as imaging biomarkers for spatial localization and monitoring early radiation response [14,15,16]. The response to radiation therapy is not known until the therapeutic course completes. With the advancement of radiation therapy-high hazard dose accumulating within the target lesion and preserving the surrounding normal tissue [18], there is increasingly important to monitor response at the earliest time point as possible
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