Spatiotemporal imaging of redox status using in vivo dynamic nuclear polarization magnetic resonance imaging system for early monitoring of response to radiation treatment of tumor
Spatiotemporal imaging of redox status using in vivo dynamic nuclear polarization magnetic resonance imaging system for early monitoring of response to radiation treatment of tumor
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DOI：
10.1016/j.freeradbiomed.2021.12.311
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发表时间：
2022-01-03
影响因子：
7.4
通讯作者：
Matsuo，Masayuki
中科院分区：
文献类型：
--
作者：
Koyasu，Norikazu;Hyodo，Fuminori;Matsuo，Masayuki
一般来说，放射治疗的有效性是通过观察治疗后CT或磁共振成像(MRI)图像的形态变化来评估的。然而，对治疗效果的评估可能非常耗时，因此可能会推迟对治疗尚未完全有效的患者病例的核实。众所周知，治疗效果取决于肿瘤组织中的氧化还原调节，这是氧化还原分子(如羟基自由基)和放射治疗产生的活性氧物种的间接作用。体内动态核极化磁共振成像(DNP-MRI)使用氨甲酰-丙氧基(CMP)作为氧化还原灵敏的DNP探针，能够基于电子和核自旋的相互作用精确监测自由基的解剖分布，即Overhauser效应。然而，肿瘤组织中氧化还原状态在照射后的时空响应仍不清楚。在这项研究中，我们使用活体DNP-MRI证明了时空氧化还原状态作为肿瘤放射后反应的早期成像生物标记物的有效性。我们的结果强调，在活体DNP-MRI/CMP使我们能够显著更快和更早地可视化肿瘤氧化还原状态的响应，与1.5T MRI观察的形态变化和超极化13C丙酮酸MRS获得的癌症代谢(Warburg效应)的验证相比，我们的研究结果表明，对活体DNP-MRI/CMP探针中的氧化还原状态变化的早期评估可能提供关于后续放射治疗有效性的非常有效的信息。
In general, the effectiveness of radiation treatment is evaluated through the observation of morphological changes with computed tomography (CT) or magnetic resonance imaging (MRI) images after treatment. However, the evaluation of the treatment effects can be very time consuming, and thus can delay the verification of patient cases where treatment has not been fully effective. It is known that the treatment efficacy depends on redox modulation in tumor tissues, which is an indirect effect of oxidizing redox molecules such as hydroxyl radicals and of reactive oxygen species generated by radiation treatment. In vivo dynamic nuclear polarization-MRI (DNP-MRI) using carbamoyl-PROXYL (CmP) as a redox sensitive DNP probe enables the accurate monitoring of the anatomical distribution of free radicals based on interactions of electrons and nuclear spin, known as Overhauser effect. However, spatiotemporal response of the redox status in tumor tissues post-irradiation remains unknown. In this study, we demonstrate the usefulness of spatiotemporal redox status as an early imaging biomarker of tumor response after irradiation usingin vivoDNP-MRI. Our results highlight thatin vivoDNP-MRI/CmP allowed us to visualize the tumor redox status responses significantly faster and earlier compared to the verification of morphological changes observed with 1.5 T MRI and cancer metabolism (Warburg effect) obtained by hyperpolarized13C pyruvate MRS. Our findings suggest that the early assessment of redox status alterations within vivoDNP-MRI/CmP probe may provide very efficient information regarding the effectiveness of the subsequent radiation treatment.