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使用代谢组学验证,在前列腺癌异种移植模型中,通过 [F]FDG 和 [C]乙酸 PET 进行放射治疗后的早期反应监测。

Early Response Monitoring Following Radiation Therapy by Using [F]FDG and [C]Acetate PET in Prostate Cancer Xenograft Model with Metabolomics Corroboration.

机构信息

Center for Advanced Molecular Imaging and Translation (CAMIT), Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.

Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.

出版信息

Molecules. 2017 Nov 10;22(11):1946. doi: 10.3390/molecules22111946.

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-[F]fluoro-d-glucose ([F]FDG) and [C]acetate ([C]ACT) positron emission tomography, with nuclear magnetic resonance (NMR) metabolomics corroboration. [F]FDG and [C]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 [F]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 [C]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 [F]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 [C]ACT PET.

摘要

我们旨在通过 2-脱氧-2-[F]氟代-d-葡萄糖 ([F]FDG) 和 [C]乙酸 ([C]ACT) 正电子发射断层扫描,结合核磁共振 (NMR) 代谢组学确证,来描绘前列腺癌小鼠模型中与早期放射治疗反应相关的代谢变化。对转染的前列腺腺癌异种移植小鼠进行 [F]FDG 和 [C]ACT PET 扫描,在照射(RT,15Gy)前后进行。通过使用离体 NMR 分析肿瘤组织的潜在代谢变化。与非 RT 组相比,RT 组肿瘤的 [F]FDG 总病变葡萄糖 (TLG) 在照射后第 1 天和第 3 天显著增加(p < 0.05)。RT(0.83 ± 0.02)和非 RT 组(0.85 ± 0.07)的 [C]ACT 最大标准摄取值 (SUVmax) 无显著差异(p > 0.05)。离体 NMR 分析显示,照射后第 3 天,RT 组葡萄糖增加 1.70 倍,乙酸增加 1.2 倍(p < 0.05)。相应地,照射后第 3 天,肿瘤细胞质乙酰辅酶 A 合成酶的表达过度表达(p < 0.05)。因此,[F]FDG 体内 PET 图像的 TLG 可描绘照射后的早期治疗反应,并成为纵向临床前研究中很有前途的预后指标。[C]ACT PET 未反映潜在的代谢变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cb5/6150287/8724ae32b05a/molecules-22-01946-g001.jpg

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