Characterizing Metabolic Heterogeneity of Hepatocellular Carcinoma with Hyperpolarized 13C Pyruvate MRI and Mass Spectrometry.

IF 5.6 Q1 ONCOLOGY
Qianhui Dou, Aaron K Grant, Patricia Coutinto de Souza, Marwan Moussa, Imad Nasser, Muneeb Ahmed, Leo L Tsai
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Abstract

Purpose To characterize the metabolomic profiles of two hepatocellular carcinoma (HCC) rat models, track evolution of these profiles to a stimulated tumor state, and assess their effect on lactate flux with hyperpolarized (HP) carbon 13 (13C) MRI. Materials and Methods Forty-three female adult Fischer rats were implanted with N1S1 or McA-RH7777 HCC tumors. In vivo lactate-to-pyruvate ratio (LPR) was measured with HP 13C MRI at 9.4 T. Ex vivo mass spectrometry was used to measure intratumoral metabolites, and Ki67 labeling was used to quantify proliferation. Tumors were first compared with three normal liver controls. The tumors were then compared with stimulated variants via off-target hepatic thermal ablation treatment. All comparisons were made using the Mann-Whitney test. Results HP 13C pyruvate MRI showed greater LPR in N1S1 tumors compared with normal liver (mean [SD], 0.564 ± 0.194 vs 0.311 ± 0.057; P < .001 [n = 9]), but not for McA-RH7777 (P = .44 [n = 8]). Mass spectrometry confirmed that the glycolysis pathway was increased in N1S1 tumors and decreased in McA-RH7777 tumors. The pentose phosphate pathway was also decreased only in McA-RH7777 tumors. Increased proliferation in stimulated N1S1 tumors corresponded to a net increase in LPR (six stimulated vs six nonstimulated, 0.269 ± 0.148 vs 0.027 ± 0.08; P = .009), but not in McA-RH7777 (eight stimulated vs six nonstimulated, P = .13), despite increased proliferation and metastases. Mass spectrometry demonstrated relatively increased lactate production with stimulation in N1S1 tumors only. Conclusion Two HCC subtypes showed divergent glycolytic dependency at baseline and during transformation to a high proliferation state. This metabolic heterogeneity in HCC should be considered with use of HP 13C MRI for diagnosis and tracking. Keywords: Molecular Imaging-Probe Development, Liver, Abdomen/GI, Oncology, Hepatocellular Carcinoma © RSNA, 2024 See also commentary by Ohliger in this issue.

用超极化13C丙酮酸核磁共振成像和质谱法表征肝细胞癌的代谢异质性
目的 描述两种肝细胞癌(HCC)大鼠模型的代谢组学特征,跟踪这些特征在肿瘤刺激状态下的演变,并通过超极化(HP)碳13(13C)磁共振成像评估它们对乳酸通量的影响。材料与方法 将 43 只成年雌性费舍尔大鼠植入 N1S1 或 McA-RH7777 HCC 肿瘤。体内质谱法用于测量瘤内代谢物,Ki67标记用于量化增殖。首先将肿瘤与三个正常肝脏对照组进行比较。然后将肿瘤与通过肝脏脱靶热消融治疗刺激的变异体进行比较。所有比较均采用 Mann-Whitney 检验。结果 HP 13C 丙酮酸核磁共振成像显示,与正常肝脏相比,N1S1 肿瘤中的 LPR 更大(平均值[SD],0.564 ± 0.194 vs 0.311 ± 0.057;P < .001 [n = 9]),但 McA-RH7777 中的 LPR 不大(P = .44 [n = 8])。质谱分析证实,N1S1 肿瘤中糖酵解途径增加,而 McA-RH7777 肿瘤中糖酵解途径减少。磷酸戊糖途径也仅在 McA-RH7777 肿瘤中减少。受刺激的 N1S1 肿瘤的增殖增加与 LPR 的净增加相对应(6 例受刺激 vs 6 例非受刺激,0.269 ± 0.148 vs 0.027 ± 0.08;P = .009),但在 McA-RH7777 肿瘤中则不然(8 例受刺激 vs 6 例非受刺激,P = .13),尽管增殖和转移增加了。质谱分析表明,只有 N1S1 肿瘤在受到刺激后乳酸生成相对增加。结论 两种 HCC 亚型在基线和向高增殖状态转化期间表现出不同的糖酵解依赖性。在使用 HP 13C MRI 进行诊断和追踪时,应考虑到 HCC 的这种代谢异质性。关键词分子成像-探针开发 肝脏 腹部/消化道 肿瘤学 肝细胞癌 © RSNA, 2024 另请参阅本期 Ohliger 的评论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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