Matsuo Masayuki, Kawai Tatsuya, Kishimoto Shun, Saito Keita, Munasinghe Jeeva, Devasahayam Nallathamby, Mitchell James B, Krishna Murali C
Radiation Biology Branch, Center for Cancer research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Department of Radiology, Gifu University Graduate School of Medicine, Gifu City, Japan.
Oncotarget. 2018 May 18;9(38):25089-25100. doi: 10.18632/oncotarget.25317.
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-C] pyruvate were performed. SCCVII and HT29 solid tumors implanted in the mouse leg were imaged by EPRI using OX063, a paramagnetic probe and C-MRI using hyperpolarized [1-C] 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 pO and metabolism was also investigated by sequential imaging of EPRI and C-MRI in HT29 tumors. A phantom study using tubes filled with different concentration of [1-C] pyruvate, [1-C] lactate, and OX063 at different levels of oxygen confirmed the validity of this sequential imaging of EPRI and hyperpolarized C-MRI. studies revealed SCCVII tumor had a significantly larger hypoxic fraction (pO < 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 (pO < 8 mmHg) 24 hours after 5-Gy irradiation was significantly higher than those without irradiation (0.76 vs. 0.36) in HT29 tumor. The study showed an increase in extracellular acidification rate after irradiation. In conclusion, co-imaging of pO and pyruvate-to-lactate conversion kinetics successfully showed the local metabolic changes especially in hypoxic area induced by radiation therapy.
为了研究肿瘤局部氧分压与能量代谢之间的关系，采用电子顺磁共振成像（EPRI）和超极化[1-C]丙酮酸的磁共振成像（MRI）进行研究。使用顺磁探针OX063通过EPRI对植入小鼠腿部的SCCVII和HT29实体瘤进行成像，并使用超极化[1-C]丙酮酸通过C-MRI进行成像。检测了两个肿瘤植入物中的局部氧分压和丙酮酸代谢情况。还通过对HT29肿瘤进行EPRI和C-MRI的序列成像，研究了单次5 Gy照射对pO和代谢的影响。一项使用装有不同浓度的[1-C]丙酮酸、[1-C]乳酸和OX063的试管在不同氧水平下进行的模型研究证实了EPRI和超极化C-MRI这种序列成像的有效性。研究显示，与HT29肿瘤相比，SCCVII肿瘤的缺氧部分（pO<8 mmHg）明显更大。SCCVII中丙酮酸向乳酸的转化通量也高于HT29。在HT29肿瘤中，5 Gy照射24小时后缺氧区域（pO<8 mmHg）的乳酸与丙酮酸比值明显高于未照射组（0.76对0.36）。该研究显示照射后细胞外酸化率增加。总之，pO与丙酮酸向乳酸转化动力学的联合成像成功显示了局部代谢变化，尤其是放疗诱导的缺氧区域的代谢变化。
