~
Hyperpolarized [1-C]Pyruvate Magnetic Resonance Spectroscopic Imaging for Evaluation of Early Response to Tyrosine Kinase Inhibition Therapy in Gastric Cancer.
机构信息
Divisionof Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA, Boston, USA.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
出版信息
Mol Imaging Biol. 2022 Oct;24(5):769-779. doi: 10.1007/s11307-022-01727-z. Epub 2022 Apr 25.
PURPOSE
To evaluate the use of hyperpolarized [1-C]pyruvate magnetic resonance spectroscopic imaging (HP-C MRSI) for quantitative measurement of early changes in glycolytic metabolism and its ability to predict response to pan-tyrosine kinase inhibitor (Pan-TKI) therapy in gastric cancer (GCa).
PROCEDURES
Pan-TKI afatinib-sensitive NCI-N87 and resistant SNU16 human GCa cells were assessed for GLUT1, hexokinase-II (HKII), lactate dehydrogenase (LDHA), phosphorylated AKT (pAKT), and phosphorylated MAPK (pMAPK) at 0-72 h of treatment with 0.1 μM afatinib. Subcutaneous NCI-N87 tumor-bearing nude mice underwent [F]FDG PET/MRI and HP-C MRSI at baseline and 4 days after treatment with afatinib 10 mg/kg/day or vehicle (n = 10/group). Changes in PET and HP-C MRSI metabolic parameters were compared between the two groups. Imaging findings were correlated with tumor growth and histopathology over 3 weeks of treatment.
RESULTS
In vitro analysis showed a continuous decrease in LDHA, pAKT, and pMAPK in NCI-N87 compared to SNU16 cells within 72 h of treatment with afatinib, without a significant change in GLUT1 and HKII in either cell type. [F]FDG PET of NCI-N87 tumors showed no significant change in PET measures at baseline and day 4 of treatment in either treatment group (SUVmean day 4/day 0: 2.7 ± 0.42/2.34 ± 0.38, p = 0.57 in the treated group vs. 1.73 ± 0.66/2.24 ± 0.43, p = 0.4 in the control group). HP-C MRSI demonstrated significantly decreased lactate-to-pyruvate ratio (L/P) in treated tumors (L/P day 4/day 0: 0.83 ± 0.30/1.10 ± 0.20, p = 0.012 vs. 0.94 ± 0.20/0.98 ± 0.30, p = 0.75, in the treated vs. control group, respectively). Response to afatinib was confirmed with decreased tumor size over 3 weeks (11.10 ± 16.50 vs. 293.00 ± 79.30 mm, p < 0.001, treated group vs. control group, respectively) and histopathologic evaluation.
CONCLUSIONS
HP-C MRSI is a more representative biomarker of early metabolic changes in response to pan-TKI in GCa than [F]FDG PET and could be used for early prediction of response to targeted therapies.
目的
评估 1-¹³C 丙酮酸磁共振波谱成像（HP-C MRSI）在定量测量早期糖酵解代谢变化中的应用，并评估其预测胃癌（GCa）对 pan-酪氨酸激酶抑制剂（Pan-TKI）治疗反应的能力。
方法
评估 Pan-TKI 阿法替尼敏感的 NCI-N87 和耐药的 SNU16 人 GCa 细胞在 0.1 μM 阿法替尼处理 0-72 h 时的 GLUT1、己糖激酶-II（HKII）、乳酸脱氢酶（LDHA）、磷酸化 AKT（pAKT）和磷酸化 MAPK（pMAPK）的表达。皮下接种 NCI-N87 肿瘤的裸鼠在接受阿法替尼 10 mg/kg/天或载体治疗 4 天后进行 [¹⁸F]FDG PET/MRI 和 HP-C MRSI（每组 n=10）。比较两组之间 PET 和 HP-C MRSI 代谢参数的变化。在治疗 3 周内，将影像学发现与肿瘤生长和组织病理学相关联。
结果
体外分析显示，与 SNU16 细胞相比，阿法替尼处理 NCI-N87 细胞 72 h 内 LDHA、pAKT 和 pMAPK 持续下降，而 GLUT1 和 HKII 在两种细胞类型中均无明显变化。NCI-N87 肿瘤的 [¹⁸F]FDG PET 在治疗组和对照组的基线和治疗第 4 天的 PET 测量均无显著变化（SUVmean day 4/day 0：2.7±0.42/2.34±0.38，p=0.57；1.73±0.66/2.24±0.43，p=0.4）。HP-C MRSI 显示治疗肿瘤的乳酸与丙酮酸比值（L/P）显著降低（L/P day 4/day 0：0.83±0.30/1.10±0.20，p=0.012；0.94±0.20/0.98±0.30，p=0.75，在治疗组与对照组之间）。经过 3 周的治疗，肿瘤体积减小证实了阿法替尼的疗效（11.10±16.50 与 293.00±79.30 mm，p<0.001，治疗组与对照组相比），同时也进行了组织病理学评估。
结论
与 [¹⁸F]FDG PET 相比，HP-C MRSI 是一种更能代表 GCa 对 pan-TKI 治疗早期代谢变化的生物标志物，可用于预测靶向治疗的反应。
Zotero 插件