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快照式癌症代谢研究:MRS(I)。

Cancer metabolism in a snapshot: MRS(I).

机构信息

Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, Spain.

Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Spain.

出版信息

NMR Biomed. 2019 Oct;32(10):e4054. doi: 10.1002/nbm.4054. Epub 2019 Jan 11.

Abstract

The contribution of MRS(I) to the in vivo evaluation of cancer-metabolism-derived metrics, mostly since 2016, is reviewed here. Increased carbon consumption by tumour cells, which are highly glycolytic, is now being sampled by C magnetic resonance spectroscopic imaging (MRSI) following the injection of hyperpolarized [1- C] pyruvate (Pyr). Hot-spots of, mostly, increased lactate dehydrogenase activity or flow between Pyr and lactate (Lac) have been seen with cancer progression in prostate (preclinical and in humans), brain and pancreas (both preclinical) tumours. Therapy response is usually signalled by decreased Lac/Pyr C-labelled ratio with respect to untreated or non-responding tumour. For therapeutic agents inducing tumour hypoxia, the C-labelled Lac/bicarbonate ratio may be a better metric than the Lac/Pyr ratio. P MRSI may sample intracellular pH changes from brain tumours (acidification upon antiangiogenic treatment, basification at fast proliferation and relapse). The steady state tumour metabolome pattern is still in use for cancer evaluation. Metrics used for this range from quantification of single oncometabolites (such as 2-hydroxyglutarate in mutant IDH1 glial brain tumours) to selected metabolite ratios (such as total choline to N-acetylaspartate (plain ratio or CNI index)) or the whole H MRSI(I) pattern through pattern recognition analysis. These approaches have been applied to address different questions such as tumour subtype definition, following/predicting the response to therapy or defining better resection or radiosurgery limits.

摘要

本文回顾了磁共振波谱成像(MRS)技术在评估癌症代谢衍生指标中的应用,主要集中在 2016 年以后。肿瘤细胞高度糖酵解,消耗大量碳,目前可以通过注射 1- 13 C-丙酮酸(Pyr)后,进行 13 C 磁共振波谱成像(MRSI)来检测。在前列腺癌(临床前和人体)、脑癌和胰腺癌(均为临床前)的研究中,随着癌症的进展,已经观察到 Pyr 和乳酸(Lac)之间的热点区域,其特征为乳酸脱氢酶活性或流量增加。与未经治疗或无反应的肿瘤相比,治疗后 Lac/Pyr 13 C 标记比通常会降低,提示治疗反应。对于诱导肿瘤缺氧的治疗药物,13 C 标记的 Lac/碳酸氢盐比可能是比 Lac/Pyr 比更好的指标。 13 C MRSI 可能会从脑肿瘤中采样细胞内 pH 值变化(抗血管生成治疗时酸化,快速增殖和复发时碱化)。肿瘤代谢组学的稳态模式仍在用于癌症评估。用于评估的指标包括单一代谢物的定量(如突变 IDH1 胶质细胞瘤中的 2-羟基戊二酸)、选定的代谢物比(如总胆碱与 N-乙酰天门冬氨酸(普通比或 CNI 指数))或通过模式识别分析的整个 1 H MRSI(I) 图谱。这些方法已应用于解决不同问题,如肿瘤亚型定义、治疗反应的预测、更好的切除或放射外科界限的定义。

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