Co-imaging of the tumor oxygenation and metabolism using electron paramagnetic resonance imaging and 13-C hyperpolarized magnetic resonance imaging before and after irradiation.
Co-imaging of the tumor oxygenation and metabolism using electron paramagnetic resonance imaging and 13-C hyperpolarized magnetic resonance imaging before and after irradiation.
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DOI：
10.18632/oncotarget.25317
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发表时间：
2018-05-18
期刊：
影响因子：
--
通讯作者：
Krishna MC
中科院分区：
文献类型：
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作者：
Matsuo M;Kawai T;Kishimoto S;Saito K;Munasinghe J;Devasahayam N;Mitchell JB;Krishna MC
为了检查肿瘤局部氧分压与能量代谢之间的关系，进行了电子顺磁共振成像（EPRI）和超极化[1- 13 C]丙酮酸盐磁共振成像（MRI）。植入小鼠腿中的SCCVII和HT 29实体瘤通过EPRI使用OX 063（顺磁探针）和使用超极化[1- 13 C]丙酮酸盐的13 C-MRI成像。局部氧分压和丙酮酸代谢的两个肿瘤植入物进行了检查。还通过HT 29肿瘤的EPRI和13 C-MRI连续成像研究了单剂量5-戈伊照射对pO 2和代谢的影响。使用填充有不同浓度的[1- 13 C]丙酮酸盐、[1- 13 C]乳酸盐和OX 063的管在不同氧气水平下进行的体模研究证实了EPRI和超极化13 C-MRI的这种顺序成像的有效性。体内研究显示，与HT 29肿瘤相比，SCCVII肿瘤具有显著更大的缺氧分数（pO 2 < 8 mmHg）。SCCVII中乳酸盐至乳酸盐转化的通量也高于HT 29。HT 29肿瘤经5-戈伊照射后24小时，低氧区（pO 2 < 8 mmHg）乳酸/丙酮酸比值（0.76 vs.0.36）显著高于对照组。体外研究表明，照射后细胞外酸化率增加。总之，pO 2和乳酸-乳酸转化动力学的联合成像成功地显示了局部代谢变化，特别是在放疗诱导的缺氧区域。
To examine the relationship between local oxygen partial pressure and energy metabolism in the tumor, electron paramagnetic resonance imaging (EPRI) and magnetic resonance imaging (MRI) with hyperpolarized [1-13C] pyruvate were performed. SCCVII and HT29 solid tumors implanted in the mouse leg were imaged by EPRI using OX063, a paramagnetic probe and 13C-MRI using hyperpolarized [1-13C] pyruvate. Local partial oxygen pressure and pyruvate metabolism in the two tumor implants were examined. The effect of a single dose of 5-Gy irradiation on the pO2 and metabolism was also investigated by sequential imaging of EPRI and 13C-MRI in HT29 tumors. A phantom study using tubes filled with different concentration of [1-13C] pyruvate, [1-13C] lactate, and OX063 at different levels of oxygen confirmed the validity of this sequential imaging of EPRI and hyperpolarized 13C-MRI. In vivo studies revealed SCCVII tumor had a significantly larger hypoxic fraction (pO2 < 8 mmHg) compared to HT29 tumor. The flux of pyruvate-to-lactate conversion was also higher in SCCVII than HT29. The lactate-to-pyruvate ratio in hypoxic regions (pO2 < 8 mmHg) 24 hours after 5-Gy irradiation was significantly higher than those without irradiation (0.76 vs. 0.36) in HT29 tumor. The in vitro study showed an increase in extracellular acidification rate after irradiation. In conclusion, co-imaging of pO2 and pyruvate-to-lactate conversion kinetics successfully showed the local metabolic changes especially in hypoxic area induced by radiation therapy.